Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2017; 23(32): 5945-5953
Published online Aug 28, 2017. doi: 10.3748/wjg.v23.i32.5945
Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population
Jin-Hua Shan, Xiao-Juan Bai, Lu-Lu Han, Yuan Yuan, Xue-Feng Sun
Jin-Hua Shan, Department of Gerontology and Geriatrics, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Xiao-Juan Bai, Lu-Lu Han, Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Yuan Yuan, Department of Tumor Research, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Xue-Feng Sun, Department of Kidney, General Hospital of Chinese People’s Liberation Army, Beijing 100853, China
ORCID number: Jin-Hua Shan (0000-0002-1130-0784); Xiao-Juan Bai (0000-0003-3890-8391); Lu-Lu Han (0000-0002-8306-4506); Yuan Yuan (0000-0002-9314-3371); Xue-Feng Sun (0000-0002-6569-6737).
Author contributions: Shan JH and Bai XJ conceptualized and designed the study; Shan JH and Han LL collected the data; Shan JH and Bai XJ performed analysis and interpretation of the data; Shan JH drafted the manuscript; Bai XJ and Sun XF obtained funding support; Yuan Y provided administrative, technical and material support.
Supported by the National Basic Research Program of China (973 Program), No. 2007CB507405, No. 2013CB530803 and No. 2013CB530804.
Institutional review board statement: This study was reviewed and approved by the Medical Ethics Committees of the General Hospital of Chinese People’s Liberation Army and China Medical University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Xiao-Juan Bai, Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China. baixj@sj-hospital.org
Telephone: +86-24-23516346
Received: April 14, 2017
Peer-review started: April 17, 2017
First decision: May 16, 2017
Revised: May 29, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: August 28, 2017

Abstract
AIM

To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori (H. pylori) infection in a healthy population, and explore factors associated with gastric biomarkers.

METHODS

Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student’s t-test, ANOVA, Pearson’s correlation and multiple linear regressions.

RESULTS

PGII levels were higher in the ≥ 65-years-old age group (P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group (P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher (P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group (P < 0.05) for H. pylori-infected subjects and 45-64-years-old age group (P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII (P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 (P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 (P = 0.005, P = 0.026).

CONCLUSION

PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

Key Words: Helicobacter pylori antibody, Pepsinogen, Gastrin, Gastric ageing

Core tip: Our study showed that in an entire healthy population, levels of serum pepsinogen (PG) II increased while PGI/PGII declined with age. We discovered that Helicobacter pylori (H. pylori) infection had an effect on raising levels of low-density lipoprotein cholesterol to increase the risk of atherosclerosis in males, especially those who are elderly. We also found that age, H. pylori infection, serum levels of renal function indicators and fasting blood glucose (FBG) were associated with levels of serum PGs and gastrin; it was assumed that they may influence the secretory function of gastric mucosa and that abnormal serum levels of FBG and renal function might participate in the occurrence and development of gastric diseases.



INTRODUCTION

Ageing of the gastric tract is an early manifestation of overall ageing, and mainly presents as a decline in the secretory function of the gastric mucosa. Histomorphological studies have demonstrated that atrophy of gastric mucosa increases with age[1-3]. In addition, studies have also shown that Helicobacter pylori (H. pylori) infection plays an important role in the progression of gastric mucosa lesions[4]. It has been demonstrated that the prevalence of H. pylori infection increases with age, and H. pylori is closely related with the occurrence and development of peptic ulcers, chronic atrophic gastritis and gastric cancer[5,6].

Serum pepsinogen (PG) levels reflect the number of glands and cells in gastric corpus mucosa. Therefore, they can reflect the secretory function of the gastric mucosa[7-10]. It has been reported that the levels of serum PGs are influenced by age, sex, pathophysiologic status of gastric mucosa and H. pylori infection[11]. Thus, serum PGs are indicators of the functional and morphological status of gastric corpus mucosa, and lower serum levels of PGI or PGI/PGII represent existence and degree of atrophy in gastric corpus mucosa[12].

Serum level of gastrin-17 (G-17) can act as a biomarker that reflects the function and structure of gastric antral mucosa. Combining serum PG and G-17 levels has been shown to provide diagnostic information on gastric mucosa[13-16], and may also reflect the degree of gastric aging. Non-invasive biomarker tests may, therefore, evaluate the secretory function of gastric mucosa and differentiate pathological conditions, such as H. pylori-associated gastritis and atrophic gastritis, from the healthy condition by combining tests for PGs, G-17 and H. pylori-immunoglobulin G (Hp-IgG)[17].

Previous studies have investigated patients with peptic ulcer, chronic atrophic gastritis and gastric cancer. To date, few studies have observed levels of the aforementioned biomarkers and effects of H. pylori infection in a healthy ageing population nor explored the associated factors. In our study, we selected PGs and G-17 as gastric biomarkers and measured their serum levels along with Hp-IgG. The aim of the current study was to observe changes in gastric biomarker levels with age in a healthy Chinese population and effects of H. pylori infection on biochemical tests, as well as to explore associated factors which influence the levels of gastric biomarkers.

MATERIALS AND METHODS
Study subjects

This was a cross-sectional study of a healthy population, defined as having no respiratory, cardiovascular, digestive, neurological, endocrine or urinary system diseases, as well as having absence of neoplastic and chronic infectious diseases and no history of psychiatric disorders. We screened 505 healthy persons out of 1500 volunteers in Shenyang, China between September 2007 and June 2008. The screening included inquiries on medical history, symptoms, smoking, alcohol intake, diet and family history obtained by a questionnaire that was completed by each participant. Physical examinations (i.e., electrocardiogram, chest radiograph, etc.) were carried out along with biochemical tests, including assessments of fasting blood glucose (FBG), blood lipids, liver function, renal function and uric acid levels.

A total of 395 subjects (168 males and 227 females) out of the 505 persons, having a mean age of 59.4 years (range: 37-87 years), were enrolled from November 2010 to May 2011 by the same screening method. Patients with circulatory, respiratory, endocrine, neurological, digestive, urinary diseases and chronic infections or neoplastic diseases, or abnormal physical examinations and test results, as well as those with psychiatric disorders or who were unable to complete instructions and self-evaluations were excluded. Blood samples were obtained and sera were stored (within 2 h of collection) at -75 °C until use for measurement of gastric biomarker levels (within 6 mo).

Informed consent was obtained from each participant. This study was reviewed and approved by the Medical Ethics Committees of General Hospital of Chinese People's Liberation Army and China Medical University.

Serological assays

Serum PGI and PGII, G-17 and H. pylori antibody levels were measured with enzyme-linked immunosorbent assay (ELISA)[18] (Biohit Oyj, Laippatie 1, FIN-00880 Helsinki, Finland). All procedures were carried out according to the manufacturer’s instructions.

Study groups

Subjects were divided into five age groups (35-44, 45-54, 55-64, 65-74 and ≥ 75 years). Hp-IgG-positive or -negative groups (Hp-IgG-positive defined as serum Hp-IgG ≥ 35 EIU)[19] were also established.

Statistical analysis

Serum biomarker levels and serum biochemical tests were analyzed in H. pylori-positive and H. pylori-negative patients, separately in male and female subjects, by Student’s t-test. Levels of serum gastric biomarkers among age groups and levels of serum gastric biomarkers and biochemical tests among age groups divided by H. pylori infection status were compared by ANOVA, and multiple comparisons were carried out by the Bonferroni method (homogeneity of variance) or Tamhane method (heterogeneity of variance). Relationships among serum gastric biomarker levels, age and biochemical tests were analyzed by Pearson’s correlation coefficient matrix. Serum gastric biomarkers as dependent variables and other related factors as independent variables were analyzed by multiple linear regression analysis with stepwise method and multiple-colinearity. For all statistical analyses, we used SPSS V.17.0, and a two-sided P value of < 0.05 was considered statistically significant.

RESULTS
Comparison of serum gastric biomarker levels in various age groups

There was no significant difference in serum levels of PGI and G-17 between each age group with increasing age. In contrast, serum levels of PGII increased with age, and were significantly higher in subjects ≥ 65-years-old compared to the 35-44-years-old group (P = 0.024, P = 0.004). The ratio of PGI/PGII decreased with age and was significantly lower in subjects ≥ 75-years-old compared to those in the 35-44-years-old group (P = 0.035) (Table 1 and Figure 1).

Table 1 Comparison of serum gastric biomarker levels in various age groups.
35-44 yr, n = 5845-54 yr, n = 8455-64 yr, n = 11765-74 yr, n = 76≥ 75 yr, n = 60FP value
PGI, μg/L92.98 ± 5.1698.47 ± 4.1598.65 ± 3.66108.56 ± 8.01117.04 ± 8.302.3260.056
PGII, μg/L9.65 ± 0.7312.26 ± 0.9112.43 ± 0.7614.23 ± 1.171a15.33 ± 1.251b3.9150.004
PGI/PGII10.94 ± 0.449.89 ± 0.409.67 ± 0.369.29 ± 0.618.71 ± 0.521a2.4070.049
G-17, pmol/L2.93 ± 0.555.10 ± 1.295.75 ± 1.499.93 ± 3.0010.03 ± 3.181.9500.101
Figure 1
Figure 1 Comparison of serum gastric biomarker levels in various age groups. There was no significant difference in serum levels of PGI and G-17 between each age group with increasing age. In contrast, serum levels of PGII increased with age, and were significantly higher in subjects ≥ 65-years-old compared to 35-44-years-old group. The ratio of PGI/PGII decreased with age, and was significantly lower in subjects ≥ 75-years-old compared to 35-44-years-old group. The “a” denotes comparison with 35-44-years-old age group, aP < 0.05, bP < 0.01. G-17: Gastrin-17; PGI: Pepsinogen I; PGII: Pepsinogen II.
Comparison of serum gastric biomarker levels by H. pylori infection status

Compared to non-infected subjects, serum levels of PGI, PGII and G-17 were significantly higher (P < 0.001, P < 0.001, P = 0.025), while the ratio of PGI/PGII was significantly lower (P < 0.001), in the H. pylori-infected subjects (Figure 2).

Figure 2
Figure 2 Comparison of serum gastric biomarker levels by Helicobacter pylori infection status. Compared to non-infected subjects, serum levels of PGI, PGII and G-17 were significantly higher, while the ratio of PGI/PGII was significantly lower in Helicobacter pylori-infected subjects. aP < 0.05, bP < 0.01. G-17: Gastrin-17; PGI: Pepsinogen I; PGII: Pepsinogen II.
Comparison of serum biochemical tests between H. pylori infection statuses by sex

There was no significant difference in serum levels of biochemical tests between H. pylori-infected and non-infected female subjects. In males, levels of low-density lipoprotein cholesterol (LDL-C) were higher (P = 0.009) in H. pylori-infected subjects compared to non-infected subjects (Table 2).

Table 2 Comparison of serum biochemical tests between Helicobacter pylori infection statuses by sex.
Male
Female
Hp-IgG (+), n = 81Hp -IgG (-), n = 87P valueHp-IgG (+), n = 104Hp-IgG (-), n = 123P value
TG, mmol/L1.33 ± 0.111.30 ± 0.170.8751.24 ± 0.061.26 ± 0.060.767
TC, mmol/L5.07 ± 0.114.80 ± 0.090.0525.16 ± 0.095.42 ± 0.090.050
HDL-C, mmol/L1.31 ± 0.041.35 ± 0.030.3811.52 ± 0.031.54 ± 0.030.575
LDL-C, mmol/L3.30 ± 0.102.99 ± 0.070.0093.26 ± 0.093.48 ± 0.080.071
FBG, mmol/L5.45 ± 0.095.26 ± 0.060.0735.29 ± 0.065.27 ± 0.090.857
Cr, μmol/L72.58 ± 1.7673.26 ± 1.400.76060.66 ± 2.5955.34 ± 0.890.054
Cys-C, mg/L0.93 ± 0.020.91 ± 0.020.5200.88 ± 0.030.81 ± 0.020.059
UA, μmol/L339.05 ± 8.19337.48 ± 9.040.898265.13 ± 6.19273.22 ± 5.300.319
Comparison of serum gastric biomarker levels and biochemical tests in various age groups by H. pylori infection status

There was no significant difference in serum levels of gastric biomarkers between each age group with increasing age in H. pylori-infected subjects. In non-infected subjects, levels of serum PGII increased with age and were significantly higher in subjects ≥ 75-years-old compared to subjects between 35- and 54-years-old (P = 0.007, P = 0.004).

In H. pylori-infected subjects, serum levels of total cholesterol (P = 0.002, P = 0.001) and LDL-C (P = 0.016, P = 0.002) were significantly higher in subjects between 55- and 74-years-old compared to those in the 35-44-years-old age group. In non-infected subjects, serum levels of total cholesterol (P = 0.023, P = 0.035) and LDL-C (P = 0.015, P = 0.006) were significantly higher in subjects between 45- and 64-years-old compared to those in the 35-44-years-old group (Table 3 and Figure 3).

Table 3 Comparison of serum gastric biomarker levels and biochemical tests in various age groups by Helicobacter pylori infection status.
35-44 yr45-54 yr55-64 yr65-74 yr≥ 75 yrFP value
n1 = 21n1 = 39n1 = 57n1 = 36n1 = 33
n2 = 37n2 = 45n2 = 60n2 = 40n2 = 27
PGI, μg/L
Hp-IgG (+)89.43 ± 7.46100.03 ± 6.4590.25 ± 5.1092.61 ± 12.2394.95 ± 13.470.8240.920
Hp-IgG (-)83.6 ± 6.4781.28 ± 3.8983.96 ± 5.0496.67 ± 10.31105.49 ± 8.081.7300.143
PGII, μg/L
Hp-IgG (+)14.68 ± 1.0818.45 ± 1.3417.47 ± 1.1619.52 ± 1.4619.51 ± 1.911.3930.260
Hp-IgG (-)6.80 ± 0.586.89 ± 0.417.64 ± 0.469.46 ± 1.4210.23 ± 0.761b2b1.1150.011
PGI/PGII
Hp-IgG (+)7.92 ± 0.537.17 ± 0.397.03 ± 0.386.65 ± 0.586.97 ± 0.520.6620.616
Hp-IgG (-)12.66 ± 0.4112.25 ± 0.4212.18 ± 0.3911.68 ± 0.8910.85 ± 0.801.1630.353
G-17, pmol/L
Hp-IgG (+)4.11 ± 0.749.81 ± 2.588.18 ± 2.177.16 ± 0.9513.7 ± 4.791.2580.285
Hp-IgG (-)2.26 ± 0.731.02 ± 0.263.44 ± 2.0312.43 ± 5.655.54 ± 3.902.2540.066
TC, mmol/L
Hp-IgG (+)4.42 ± 0.144.96 ± 0.145.30 ± 0.111b5.51 ± 0.191b5.00 ± 0.156.604< 0.001
Hp-IgG (-)4.77 ± 0.105.41 ± 0.171a5.35 ± 0.131a5.18 ± 0.164.98 ± 0.142.7090.031
LDL-C, mmol/L
Hp-IgG (+)2.71 ± 0.143.10 ± 0.123.40 ± 0.111a3.60 ± 0.171b2a3.17 ± 0.147.291< 0.001
Hp-IgG (-)2.89 ± 0.093.47 ± 0.151a3.48 ± 0.111b3.33 ± 0.133.08 ± 0.133.5440.008
FBG, mmol/L
Hp-IgG (+)5.25 ± 0.085.22 ± 0.135.38 ± 0.125.46 ± 0.125.44 ± 0.080.7910.532
Hp-IgG (-)5.01 ± 0.065.21 ± 0.085.29 ± 0.085.34 ± 0.085.39 ± 0.341.1860.318
Cr, μmol/L
Hp-IgG (+)56.95 ± 2.5760.38 ± 2.3563.79 ± 1.7163.61 ± 3.0481.4 ± 7.241a4.9740.001
Hp-IgG (-)59.19 ± 2.0562.78 ± 1.9561.20 ± 1.6763.53 ± 2.2973.19 ± 3.401b2a3b4.1740.003
Cys-C, mg/dL
Hp-IgG (+)0.69 ± 0.020.78 ± 0.021a0.84 ± 0.021b0.97 ± 0.031b2b3a1.19 ± 0.071b2b3b19.952< 0.001
Hp-IgG (-)0.71 ± 0.020.78 ± 0.020.83 ± 0.021b0.93 ± 0.031b2b1.14 ± 0.041b2b3b4b28.435< 0.001
Figure 3
Figure 3 Comparison of serum cholesterol levels in various age groups by Helicobacter pylori infection status. In H. pylori-infected subjects, serum levels of TC and LDL were significantly higher in subjects between 55- and 74-years-old compared to those in the 35-44-years-old age group. In non-infected subjects, serum levels of TC and LDL were significantly higher in subjects between 45- and 64-years-old compared to those in the 35-44-years-old age group. The “a” denotes comparison with the 35-44-years-old age group and the “b” denotes comparison with the 45-54-years-old age group, aP < 0.05, bP < 0.01. H. pylori: Helicobacter pylori; LDL-C: Low-density lipoprotein cholesterol; TC: Total cholesterol.
Correlation analysis among serum gastric biomarker levels, age and biochemical tests

Age positively correlated with serum levels of Hp-IgG, PGI, PGII and G-17 (P = 0.038, P = 0.001, P < 0.001, P = 0.005) and negatively correlated with ratio of PGI/PGII (P = 0.002). Levels of serum Hp-IgG positively correlated with serum levels of PGI, PGII and G-17 (P < 0.001, P < 0.001, P = 0.038) and negatively correlated with ratio of PGI/PGII (P < 0.001).

Levels of serum PGI positively correlated with serum levels of uric acid, creatinine and cystatin-C (P < 0.001, P < 0.001, P < 0.001). Levels of serum PGII positively correlated with serum levels of creatinine and cystatin-C (P < 0.001, P < 0.001). Levels of serum G-17 positively correlated with serum levels of FBG, creatinine and cystatin-C (P = 0.018, P = 0.011, P = 0.037).

Levels of serum Hp-IgG were strongly associated with serum levels of PGII and PGI/PGII (r = 0.592, P < 0.001; r = -0.587, P < 0.001), and levels of serum PGII were strongly associated with serum levels of PGI and PGI/PGII (r = 0.682, P < 0.001; r = -0.588, P < 0.001)(Table 4).

Table 4 Correlation matrix among serum gastric biomarker levels, age and biochemical tests.
AgePGIPGIIPGI/IIG-17Hp-IgGTGTCHDL-CLDL-CFBGUACrCys-CBMI
Age10.161b0.215b-0.155b0.140b0.104a-0.0090.108a0.0100.136b0.145b0.148b0.265b0.548b-0.016
0.0010.0000.0020.0050.0380.8540.0330.8440.0070.0040.0030.0000.0000.781
PGI1.0000.682b0.047-0.140b0.260b-0.014-0.066-0.051-0.0230.0560.188b0.301b0.355b0.011
0.0000.3570.0050.0000.7880.1880.3080.6540.2660.0000.0000.0000.843
PGII1.000-0.588b0.149b0.592b-0.029-0.062-0.075-0.019-0.0050.0770.209b0.278b0.006
0.0000.0030.0000.5710.2160.1350.7050.9150.1240.0000.0000.913
PGI/II1.000-0.384b-0.587b0.0350.0320.0400.0270.0740.080-0.019-0.0600.003
0.0000.0000.4880.5320.4270.5900.1400.1120.7120.2340.961
G-171.0000.105a0.055-0.020-0.068-0.0160.119a-0.0620.129a0.105a-0.023
0.0380.2790.6950.1770.7490.0180.2190.0110.0370.690
Hp- IgG1.0000.000-0.025-0.062-0.0040.0570.0090.0580.0950.006
0.9850.6180.2200.9380.2570.8650.2500.0590.919
TG1.0000.278b-0.327b0.145b0.166b0.156b0.0590.0680.048
0.0000.0000.0040.0010.0020.2430.1760.402
TC1.0000.295b0.896b0.123a0.023-0.032-0.0390.111
0.0000.0000.0150.6470.5300.4420.053
HDL-C1.0000.032-0.093-0.282b-0.176b-0.164b0.017
0.5280.0640.0000.0000.0010.762
LDL-C1.0000.149b0.0740.0000.0220.085
0.0030.14210.0000.6640.138
FBG1.0000.119a0.111a0.0860.034
0.0180.0270.0860.558
UA1.0000.465b0.403b-0.003
0.0000.0000.961
Cr1.0000.706b-0.010
0.0000.858
Cys-C1.000-0.026
0.648
BMI1.000
Analysis of factors associated with serum levels of gastric biomarkers

With serum PGI as a dependent variable, serum levels of creatinine, Hp-IgG and FBG positively correlated with levels of serum PGI (P < 0.001, P < 0.001, P = 0.037), while serum levels of G-17 negatively correlated with levels of serum PGI (P < 0.001). With serum PGII as a dependent variable, serum levels of creatinine, Hp-IgG and age positively correlated with levels of serum PGII (P = 0.006, P < 0.001, P = 0.007). With PGI/PGII as a dependent variable, serum levels of FBG positively correlated with PGI/PGII (P < 0.001), while serum levels of Hp-IgG, G-17 and age negatively correlated with PGI/PGII (P < 0.001, P < 0.001, P = 0.024). With serum G-17 as a dependent variable, age and serum levels of creatinine, Hp-IgG and FBG positively correlated with levels of serum G-17 (P = 0.032, P < 0.001, P = 0.037, P = 0.045), while serum levels of PGI and uric acid negatively correlated with levels of serum G-17 (P < 0.001, P = 0.009)(Table 5).

Table 5 Factors associated with serum levels of gastric biomarkers.
Dependent variableAssociated factorsNon-standard coefficient
Standard coefficientP value
BSEβ
PGIConstant50.347200.8450.798
Cr0.7120.1380.2730.000
Hp-IgG0.3340.0660.2630.000
G-17-0.6470.138-0.2470.000
FBG70.85930.7440.1100.037
PGIIConstant-10.65720.0780.426
Hp-IgG0.1200.0100.5560.000
Cr0.0580.0210.1310.006
Age0.0890.0330.1290.007
PGI /PGIIConstant90.25110.4610.000
Hp-IgG-0.0540.004-0.5200.000
G-17-0.0750.009-0.3490.000
FBG10.0370.2550.1770.000
Age-0.0330.015-0.1010.024
G-17Constant-140.81780.9920.100
Age0.1920.0890.12400.032
PGI-0.1030.022-0.2690.000
Cr0.2280.0630.2280.000
Hp-IgG0.0580.0270.1190.037
UA-0.0420.016-0.1600.009
FBG30.05410.5200.1120.045
DISCUSSION

A European gastric biomarkers test[17] has been developed to measure serum PG and G-17 levels, and Hp-IgG antibodies by ELISA technique. Compared to endoscopic biopsy findings, the test classified the subjects into groups with “healthy” or “diseased” gastric mucosa with 94% accuracy, 95% sensitivity and 93% specificity. Compared to endoscopic histological findings, the accuracy of the biomarkers test in diagnosing atrophic gastritis was 87%, with a sensitivity of 40% and a specificity of 94%. Combined testing of Hp-IgG, PG and G-17 levels is of great clinical significance for general assessment of gastric mucosa secretion.

It has been previously shown that levels of serum PGI decreased with age. Levels of serum PGII increased with age, but declined in participants aged over 60. Ratio of PGI/PGII decreased with age, but it increased after age 60[20]. It has also been observed that levels of PGI and PGII increased with age. In a healthy population, levels of PGI and PGII varied amongst age groups, and the average PG level was highest in the senile group[21].

Our study showed that in the entire healthy study population, levels of serum PGII increased with age, while the ratio of PGI/PGII decreased with age. The correlation between age and PGII is stronger and more significant than that of PGI; possibly, the distribution of PGII-secreting cells is more extensive, and this could be one of the reasons to explain this finding. Since the ratio of PGI/PGII reflects the degree of atrophy in gastric mucosa, the current study indicated that atrophy of gastric mucosa occurred and developed with increasing age in a non-invasive serological method.

It has been suggested that serum levels of PGI and PGII significantly correlated with age in H. pylori-positive subjects. Increased PGI and PGII levels associated with age in a healthy population were caused by increased rates of H. pylori infection. Levels of PGI and PGII were dependent on the presence of H. pylori infection[22]. It was suggested that serum levels of G-17, PGI and PGII increased in subjects with H. pylori infection, especially PGII, while the ratio of PGI/PGII decreased.

Hypergastrinemia and hyperpepsinogenemia may be secondary to H. pylori infection[23,24]. The results of the current study on the effects of H. pylori infection on serum gastric biomarker levels were consistent with those of previous studies, and it was suggested that H. pylori infection had a closer correlation with PGII than with PGI and may influence the levels of PGII more.

It has been shown that H. pylori infection was independently associated with elevated LDL-C levels and contributed to the atherosclerotic process[25]. The current study showed the difference on levels of serum LDL-C between H. pylori-infected and non-infected male subjects, which suggested an effect of H. pylori infection on raising levels of LDL-C in males. Meanwhile, the highest level of LDL-C was found in the middle-aged group (45-64 years) in non-infected subjects, while in H. pylori-infected subjects it was found in the elderly group (55-74 years). Increased LDL-C level is a risk factor for the development of atherosclerosis, and the current study indicated that Hp infection may increase the risks of atherosclerosis in males, especially those of elderly age.

It has been reported that renal function status may influence levels of serum PG and gastrin. Levels of serum PG and gastrin were found to be increased in patients with renal function insufficiency. This may have been due to reduced renal clearance of PG and gastrin[26,27]. There have been few studies investigating the relationship between renal function and serum PG and gastrin in a healthy population. The current study showed that age and serum levels of Hp-IgG, creatinine and FBG were the main factors associated with levels of serum PG and G-17. Since different levels of PG and G-17 represent different pathophysiological status of gastric mucosa, it was assumed that age, H. pylori infection, and serum levels of FBG and markers of renal function may influence the secretory function of gastric mucosa, and that abnormal serum levels of FBG and renal function might participate in the occurrence and development of gastric diseases.

In summary, the current study observed changes in gastric biomarker levels with age and effects of H. pylori infection in a healthy Chinese population, and explored factors associated with gastric biomarkers. Our data provide a theoretical basis for the recognition of gastric aging and its related diseases, which is of important clinical significance. However, there are some limitations in the study. Firstly, the sample size was relatively small and may, therefore, not represent the whole healthy population. Secondly, we found the effects of H. pylori infection and the correlation between gastric biomarkers and other associated factors, but the mechanisms are not clear. More studies are needed to illustrate the mechanisms in the future.

COMMENTS
Background

Combined testing of Helicobacter pylori (H. pylori)-immunoglobulin G (Hp-IgG), pepsinogen (PG) and G-17 levels is of great clinical significance for general assessment of gastric mucosa secretion, and may also reflect the degree of gastric aging. Previous studies have investigated patients with peptic ulcer, chronic atrophic gastritis and gastric cancer. To date, few studies have observed levels of the gastric biomarkers and effects of H. pylori infection in a healthy ageing population nor explored the associated factors.

Research frontiers

Non-invasive biomarker tests may evaluate the secretory function of gastric mucosa, and distinguish pathological conditions, such as atrophic gastritis, from the healthy condition by combining tests for PGs, G-17 and Hp-IgG. Lower serum levels of PGI or PGI/PGII represent existence and degree of atrophy in gastric corpus mucosa. Studies have indicated that serum levels of PGs and G-17 are related to H. pylori infection and age, and could be significantly influenced by H. pylori infection. Furthermore, it has been shown that H. pylori infection was independently associated with elevated low-density lipoprotein cholesterol (LDL-C) levels and contributed to the atherosclerotic process.

Innovations and breakthroughs

The current study observed changes in gastric biomarker levels with age and effects of H. pylori infection in a healthy Chinese population, and explored factors associated with gastric biomarkers. This study showed that in the entire healthy study population, levels of serum PGII increased while PGI/PGII declined with age, which indicated that atrophy of gastric mucosa occurred and developed with increasing age, observed via a non-invasive serological method. Meanwhile, we discovered that H. pylori infection had an effect on raising levels of LDL-C to increase the risk of atherosclerosis in males, especially those of elderly age. Moreover, it is suggested that age, H. pylori infection, serum levels of renal function and fasting blood glucose (FBG) were associated with levels of serum PGs and gastrin.

Applications

In this study, the authors’ discovered that H. pylori infection had an effect on raising levels of LDL-C to increase the risk of atherosclerosis in males, especially those who were elderly, which indicated that H. pylori infection should be afforded a more important status and given active treatment in elderly males to prevent atherosclerotic diseases. This study suggested that age, H. pylori infection, serum levels of renal function and FBG were associated with levels of serum PGs and gastrin. It was assumed that serum levels of renal function and FBG may influence the secretory function of gastric mucosa, and abnormal serum levels of FBG and renal function might participate in the occurrence and development of gastric diseases.

Terminology

H. pylori: A curved Gram-negative bacillus which is found in gastric mucosa; H. pylori is closely related with multiple gastric diseases, such as peptic ulcers, chronic atrophic gastritis and gastric cancer. PG: A precursor of pepsin which is mainly secreted by cells in the gastric corpus and can be divided into two groups, PGI and PGII; serum PG levels reflect the number of glands and cells, as well as the secretory function in gastric corpus mucosa. G-17: A hormone which is mainly secreted by G cells in gastric antrum and plays multiple physiological roles; serum level of G-17 reflects the number of cells and the secretory function in gastric antral mucosa.

Peer-review

The authors have carried out a detailed study of biomarkers and H. pylori infection in a large cohort of patients. The manuscript is detailed, the study well carried out and the data is comprehensive and complex.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: China

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B, B

Grade C (Good): C

Grade D (Fair): 0

Grade E (Poor): 0

P- Reviewer: Bramhall S, Lombardo L, Yamaoka Y S- Editor: Qi Y L- Editor: Filipodia E- Editor: Zhang FF

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