Case Control Study Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2022; 13(8): 643-653
Published online Aug 15, 2022. doi: 10.4239/wjd.v13.i8.643
Association of rs1137101 with hypertension and type 2 diabetes mellitus of Mongolian and Han Chinese
Xiu-Lan Su, Jing Wang, Wen-Yan Han, Hong-Wei Cui, Yun-Na Wu, Meng-Lu Yuan, Ke-Yu Zhao
Ke-Yu Zhao, Xiu-Lan Su, Clinical Medical Research Center of The Affiliated Hospital, Inner Mongolia Key Laboratory of Medical Cellular Biology, Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia Autonomous Region, China
Meng-Lu Yuan, School of Public Health, Inner Mongolia Medical University, Huhhot 010050, Inner Mongolia Autonomous Region, China
Yun-Na Wu, Medical Clinical Laboratory, Huhhot First Hospital, Huhhot 010050, Inner Mongolia Autonomous Region, China
Hong-Wei Cui, Department of Scientific Research, Inner Mongolia Autonomous Region Cancer Hospital/The Affiliated People’s Hospital of Inner Mongolia Medical University, Huhhot 010050, Inner Mongolia Autonomous Region, China
Wen-Yan Han, Clinical Medical Laboratory Center, The Second Affiliated Hospital of Inner Mongolia Medical University, Huhhot 010050, Inner Mongolia Autonomous Region, China
Jing Wang, Graduate School, Inner Mongolia Medical University, Huhhot 010050, Inner Mongolia Autonomous Region, China
ORCID number: Xiu-Lan Su (0000-0001-6527-7412).
Author contributions: Zhao KY, Yuan ML, Wu YN, Cui HW, Han WY, Wang J and Su XL designed the research study; Zhao KY, Wang J, Yuan ML and Su XL performed the research; Su XL and Zhao KY contributed new reagents and analytic tools; Zhao KY, Yuan ML and Su XL analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81260058.
Institutional review board statement: The study was reviewed and approved by the Affiliated Hospital of Inner Mongolia Medical University Institutional Review Board, No. 2015003.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiu-Lan Su, MMed, Professor, Clinical Medical Research Center of The Affiliated Hospital, Inner Mongolia Key Laboratory of Medical Cellular Biology, Inner Mongolia Medical University, No. 1 North Tongdao Road, Hohhot, 010050, Inner Mongolia Autonomous Region, China. xlsu@sina.com
Received: February 17, 2022
Peer-review started: February 17, 2022
First decision: May 30, 2022
Revised: June 14, 2022
Accepted: July 26, 2022
Article in press: July 26, 2022
Published online: August 15, 2022

Abstract
BACKGROUND

Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are often coincident, and each condition is considered a risk factor for the other. Both occur frequently in the Inner Mongolia region of China. The reasons for differences in risk between Han and Mongolian ethnic groups are not known. The LEPR gene and its polymorphism, rs1137101 (Gln223Arg), are both considered risk factors for HTN and T2DM, but any role of rs1137101 in the occurrence of HTN + T2DM remains unclear for Mongolian and Han populations in the Inner Mongolia region.

AIM

To investigate the relationship between rs1137101 and the occurrence of HTN with T2DM in Mongolian and Han populations in Inner Mongolia.

METHODS

A total of 2652 subjects of Han and Mongolian ethnic origins were enrolled in the current study, including 908 healthy controls, 1061 HTN patients and 683 HTN patients with T2DM.

RESULTS

The association between the rs1137101 polymorphism and HTN with T2DM was analyzed, and differences between Han and Mongolian individuals assessed. There was a significant correlation between rs1137101 and HTN (co-dominant, dominant, over-dominant and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) after adjustment for sex and age in individuals of Mongolian origin. rs1137101 was significantly associated with HTN (co-dominant, recessive and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) in the Han Chinese population.

CONCLUSION

Mongolian and Han subjects from Inner Mongolia with HTN who had rs1137101 were protected against the development of T2DM. Allele A has the opposite impact on the occurrence of HTN in Mongolian and Han Chinese populations.

Key Words: rs1137101, Mongolian, Han Chinese, Hypertension, Type 2 diabetes mellitus, Associate study

Core Tip: Hypertension and type 2 diabetes mellitus are often coincident, and each condition is a risk factor for the other. It is unknown why there are differences in risk between Han and Mongolian ethnic groups. The LEPR gene and its polymorphism, rs1137101 (Gln223Arg), are considered risk factors for the occurrence of hypertension and type 2 diabetes mellitus. The current study investigated the relationship between rs1137101 and the occurrence of hypertension with type 2 diabetes mellitus in Mongolian and Han populations in Inner Mongolia. Differences between the two populations were analyzed. The aim was to inform further research on advanced metabolic disease.



INTRODUCTION

The causes of hypertension (HTN) are multifactorial, and the condition is in turn a risk factor for cardiovascular disease and nephropathy[1]. Current estimates put a global figure of 1.3 billion[2,3] on the number of people with high blood pressure, an estimate that is set to rise to 1.6 billion by 2025[2,4]. Advanced age, gender, obesity and genotype are all risk factors for HTN[2]. Diabetes mellitus (DM) is another public health problem that has increased rapidly over recent years with 80%-90% patients having type 2 DM (T2DM)[5,6]. Epidemiological studies have shown that HTN is a major risk factor for T2DM[7]. One-third of HTN patients also have T2DM and are at an increased risk of cardiovascular disease and mortality[8,9].

The leptin (LEP) receptor (LEPR) is a transmembrane protein encoded by the LEPR gene. Several variants have been characterized, and there is widespread expression throughout the body’s tissues[10]. The LEP hormone is known to have roles in the regulation of hunger, energy balance, metabolism, reproduction and insulin secretion mediated by binding to LEPR[11,12]. Binding of LEP to its hypothalamic receptor has been shown to raise blood pressure in mice, and blockade of LEPR resulted in lower values[13,14]. LEPR has roles in insulin secretion, and its activity is relevant to the development of insulin resistance[12,15]. Indeed, a recent study has correlated LEPR polymorphisms with DM and HTN[16,17]. Among the Han Chinese population, the LEPR gene polymorphism, rs13306519, has been associated with DM and rs12037879 with HTN[5]. Moreover, rs1137100 (Arg109Lys) and rs8179183 (Lys656Asn) have been associated with both DM and HTN[15,18].

The LEPR gene polymorphism, rs1137101, is located on chromosome 1p31 and involves a substitution of the 223rd amino acid residue, gln (Q) for Arg (R). This mutation affects the ObRIg domain, according to the PFAM database (http://pfam.xfam.org/protein/P48357; Figure 1A and Table 1). Construction of a 3D model of the region including amino acids 126 to 533 using Swiss-model software (https://swissmodel.expasy.org/) revealed a consequent change in protein structure (Figure 1B). These predictions imply that the rs1137101 mutation may influence protein structure and have an impact on protein function. Previous studies have associated rs1137101 (Gln223Arg) with obesity, cancer, HTN and DM[9,19,20]. It also has been shown to be a risk factor for HTN and T2DM in the Chinese population[21,22]. The current study investigated the relationship between rs1137101 and the occurrence of HTN with T2DM in Mongolian and Han populations in Inner Mongolia.

Figure 1
Figure 1 Leptin receptor domains and 3D structure. A: The PFAM database obtains the domains of the leptin receptor (LEPR) protein; B: Swiss-model was used to construct the 3D model of the leptin receptor and the leptin receptor (Q223R) protein fragment 126 to 533. The red frame represented the differences between two models.
Table 1 Domain boundaries and score for each of the domains.
SourceDomainStartEndGathering threshold (bits)
Score (bits)
E-value
Sequence
Domain
Sequence
Domain
Sequence
Domain
PfamObR_Ig12623325.825.8170.561.13.50E-473.9E-13
PfamLep_receptor_Ig32942028.828.884.884.81.00E-201.00E-20
PfamObR_Ig43153325.825.8170.5112.73.50E-473.40E-29
TransmembraneNA840862NANANANANANA
Low_complexityNA849863NANANANANANA
DisorderNA924927NANANANANANA
Low_complexityNA937946NANANANANANA
DisorderNA966967NANANANANANA
DisorderNA970973NANANANANANA
DisorderNA975976NANANANANANA
DisorderNA9971001NANANANANANA
DisorderNA10641065NANANANANANA
MATERIALS AND METHODS
Study subjects

A total of 2652 subjects, including 908 healthy controls, 1061 HTN patients and 683 patients with HTN + T2DM, were randomly selected from adult residents of Mongolia (Hohhot, Wuhai, Xilinhot) and enrolled in the study. Study participants were unrelated, and the ethnic composition was 1347 Han and 1305 Mongolian. All participants provided written informed consent. The study was performed in accordance with the declaration of Helsinki and approved by the ethical committee of the affiliated hospital of Inner Mongolia Medical University.

T2DM and HTN were diagnosed according to the following criteria established by the World Health Organization: HTN: Systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or current prescription for antihypertensive medication[23]. Participants with chronic renal disease, renal artery stenosis, primary hyperaldosteronism, thyroid disease, Cushing syndrome, phaeochromocytoma or other diseases known to cause HTN were excluded; T2DM: Fasting blood sugar (FBS) ≥ 7.0 mmol /L or postprandial blood glucose ≥ 11.1 mmol/L or current definitive diagnosis of T2DM[24]. Participants with T1DM, cancer or other severe metabolic disease were excluded.

Data collection

Age, weight and medical history were collected by questionnaire. Body mass index was calculated according to the formula: Mass (kg)/height2 (m2). Blood pressure was measured on the right arm using a mercury sphygmomanometer. Blood samples of HTN, T2DM and HTN + T2DM groups were collected after an 8 h fast. Genomic DNA was isolated from whole blood using a Maga bio plus whole blood genomic DNA purification Kit II (Hangzhou Bioer Technology co. Ltd, China) according to the manufacturer’s instructions. FBS, triglyceride, cholesterol, high density lipoprotein and low density lipoprotein were measured after plasmapheresis.

Genotyping

rs1137101 (Gln223Arg) polymorphisms were assessed by PCR amplification. The primers used were forward: 5’-TTCCCCAAAAAGGCAGTTTTCA-3’ and reverse: 5’-AGAAGCCACTCTTAATACCCCCAGT-3’. The target DNA sequences were amplified using a multiplex PCR method. Thermal cycling was performed for the rs1137101 loci in Gene Amp PCR system 9600 (PerkinElmer, Waltham, MA, United States) fluorescent products of ligase detection reaction differentiated by 3130xl genetic analyzer (Applied Biosystems, CA, United States).

Statistical analysis

Statistical analysis was performed using SPSS 22.0 (IBM Corp., Armonk, NY, United States) and SNPStats (https://www.snpstats.net/start.htm)[25] software. Categorical variables were presented as frequencies. Continuous data were reported as the mean ± standard deviation. Student’s t test was used to compare age, weight, height, body mass index, FBS, systolic blood pressure, diastolic blood pressure, triglyceride, cholesterol, high density lipoprotein and low density lipoprotein and statistical hypotheses were tested using the 2-tailed t test. The χ2 test was used to analyze ethnic and gender differences. Logistic regression was used to compute the odds ratio (OR) by adjusting for age and sex and the adjusted OR is presented with 95% confidence interval. Logistic regression, Hardy Weinberg Equilibrium and five genetic models (co-dominant, dominant, recessive, over-dominant and log-additive) were calculated using SNPStats software. A value of P < 0.05 was considered to be significant.

RESULTS
Baseline demographic characteristics

Baseline demographic characteristics of the study population are summarized in Table 2. Significant differences were found in ethnicity, gender, age, weight, height, FBS, Systolic blood pressure, diastolic blood pressure and high density lipoprotein between cases with HTN, those with both HTN + T2DM and controls. No significant deviation from the Hardy Weinberg Equilibrium was detected (Table 3). Allele frequency was not significant in the Han population, but significant differences between Mongolian groups were observed (Table 4).

Table 2 Baseline characteristics.
Control, n = 908HTN, n = 1061HTN with T2DM, n = 683
P value
Control vs HTN
Control vs HTN + T2DM
HTN vs HTN + T2DM
EthnicHan455406486< 0.0001< 0.0001< 0.0001
Mongolian453655197
GenderMale357601397< 0.0001< 0.00010.542
Female551460286
Age48.11 ± 15.0654.49 ± 15.6763.89 ± 11.17< 0.0001< 0.0001< 0.0001
Weight (kg)66.14 ± 11.0672.32 ± 12.0673.35 ± 12.48< 0.0001< 0.00010.2156
Height (cm)163 ± 0.09168 ± 0.08161.26 ± 0.10< 0.00010.61100.0032
BMI (kg/m2)25.27 ± 8.5025.56 ± 3.6326.48 ± 5.120.40670.75880.8723
FBS (mmol/L)5.06 ± 0.495.73 ± 0.778.59 ± 3.370.0721< 0.0001< 0.0001
SBP (mm Hg)117.21 ± 14.27151.10 ± 18.94166.47 ± 17.53< 0.0001< 0.0001< 0.0001
DBP (mm Hg)77.20 ± 7.9588.59 ± 12.74100.84 ± 13.31< 0.0001< 0.0001< 0.0001
TG (mmol/L)1.63 ± 1.062.24 ± 1.522.59 ± 12.140.06260.00510.4768
CHO (mmol/L)4.53 ± 1.304.47 ± 3.594.52 ± 1.260.89130.99840.8885
HDL (mmol/L)1.44 ± 0.541.75 ± 0.951.27 ± 0.35< 0.0001< 0.0001< 0.0001
LDL (mmol/L)2.84 ± 1.002.87 ± 1.382.94 ± 11.10.99210.92250.9586
Table 3 Hardy Weinberg equilibrium analysis.

Group
G/G
G/A
A/A
G
A
P value
Han, n = 1347Control, n = 45535194107961140.2
HTN, n = 406312913715970.24
HTN + T2DM, n = 4863948488721000.21
Mongolian, n = 1305Control, n = 45334310197871190.68
HTN, n = 6554362021710742360.29
HTN + T2DM, n = 197151424344500.53
Table 4 Statistics of allele and genotype frequencies.
Population
Allele
All subjects count (%)
Control count (%)
HTN count (%)
HTN + T2DM count (%)
P value
Han, n = 1347G2383 (88)796 (87)715 (88)872 (90)0.288
A311 (12)114 (13)97 (12)100 (10)
A/A21 (2)10 (2)3 (1)8 (2)0.153
G/A269 (20)94 (21)91 (22)84 (17)
G/G1057 (78)351 (77)312 (77)394 (81)
Mongolian, n = 1305G2205 (84)787 (87)1074 (82)344 (87)0.002
A405 (16)119 (13)236 (18)50 (13)
A/A30 (2)9 (2)17 (3)4 (2)0.006
G/A345 (26)101 (22)202 (31)42 (21)
G/G930 (71)343 (76)436 (67)151 (77)
LEPR gene polymorphisms and HTN in ethnic Han and Mongolian Chinese

The correlation between the LEPR gene polymorphism, rs1137101, and HTN in ethnic Han and Mongolian Chinese subjects was analyzed. A total of 861 subjects of Han origin (control = 455; HTN = 406) and 1108 subjects of Mongolian origin (control = 453; HTN = 655) were assessed. Logistic regression analysis was used to evaluate whether rs1137101 was independently associated with HTN after adjusting for sex and age (Table 5). Use of five inheritance models, codominant, dominant, recessive, over-dominant and log-additive, gave the following results: Co-dominant (A/G) model: OR = 0.88 (0.62-1.27); co-dominant (A/A) model: OR = 0.21 (0.05-0.80); and recessive (A/A) model: OR = 0.21 (0.05-0.82) for hypertensive Han subjects compared with controls. Results for Mongolian subjects were: Co-dominant (A/G) model: OR = 1.49 (1.12-1.97); co-dominant (A/A) model: OR = 1.47 (0.64-3.34); dominant (A/G-A/A) model: OR = 1.49 (1.13-1.95); over-dominant (A/A) model: OR = 1.47 (1.11-1.95); and log-additive model: OR = 1.40 (1.10-1.79). An association between rs1137101 and HTN was established for subjects of Mongolian ethnic origin.

Table 5 Association of the control and hypertension groups for Han and Mongolian Chinese.
ModelGenotypeHan, n = 861
Mongolian, n = 1108
Control, n (%)
HTN, n (%)
OR (95%CI)
P value
Control, n (%)
HTN, n (%)
OR (95%CI)
P value
Co-dominantG/G351 (77.1)312 (76.8)10.041343 (75.7)436 (66.6)10.016
A/G94 (20.7)91 (22.4)0.88 (0.62-1.27)101 (22.3)202 (30.8)1.49 (1.12-1.97)
A/A10 (2.2)3 (0.7)0.21 (0.05-0.80)9 (2.0)17 (2.6)1.47 (0.64-3.34)
DominantG/G351 (77.1)312 (76.8)10.23343 (75.7)436 (66.6)10.004
A/G-A/A104 (22.9)94 (23.1)0.81 (0.57-1.15)110 (24.3)219 (33.4)1.49 (1.13-1.95)
RecessiveG/G-A/G445 (97.8)403 (99.3)10.015444 (98)638 (97.4)10.51
A/A10 (2.2)3 (0.7)0.21 (0.05-0.82)9 (2.0)17 (2.6)1.32 (0.58-2.99)
Over-dominantG/G-A/A361 (79.3)315 (77.6)10.63352 (77.7)453 (69.2)10.0064
A/G94 (20.7)91 (22.4)0.91 (0.64-1.31)101 (22.3)202 (30.8)1.47 (1.11-1.95)
Log-additive---0.75 (0.55-1.04)0.082--1.40 (1.10-1.79)0.0059
The correlation between rs1137101 and HTN with T2DM in Han and Mongolian subjects

The association of rs1137101 with HTN + T2DM was analyzed. A total of 683 subjects, composed of 197 Mongolian and 486 Han, were included. The same five genetic models, codominant, dominant, recessive, over-dominant and log-additive, were used to analyze associations between HTN + T2DM as described above for HTN. OR (adjusted for sex and age) for the five genetic models in Mongolian subjects were: Co-dominant (A/G): 0.70 (0.44-1.11); co-dominant (A/A): 1.06 (0.27-4.25); dominant (A/G-A/A): 0.72 (0.46-1.13); recessive (G/G-A/G):1.15 (0.29-4.57); over-dominant (A/G): 0.70 (0.44-1.11); and log-additive: 0.78 (0.52-1.16). OR (adjusted for sex and age) for the five genetic models in Han subjects were: Co-dominant (A/G): 0.59 (0.40-0.87); co-dominant (A/A): 0.38 (0.14-1.08); dominant (A/G-A/A): 0.56 (0.39-0.82); recessive (G/G-A/G): 0.43 (0.15-1.21); over-dominant (A/G): 0.61 (0.41-0.89); and log-additive: 0.60 (0.43-0.83). No significant differences were found in Mongolian subjects, but the genotypes GA and AA significantly decreased the risk of HTN + T2DM in Han subjects (Table 6). Thus, the LEPR polymorphism is associated with the occurrence of HTN + T2DM in Han Chinese populations but not in Mongolian Chinese.

Table 6 Association of rs1137101 with hypertension + type 2 diabetes mellitus (control vs hypertension + type 2 diabetes mellitus).
ModelGenotypeHan, n = 941
Mongolian, n = 650
Control, n (%)
HTN with T2DM, n (%)
OR (95%CI)
P value
Control, n (%)
HTN with T2DM, n (%)
OR (95%CI)
P value
Co-dominantG/G351 (77.1)394 (81.1)10.0075343 (75.7)151 (76.7)10.3
A/G94 (20.7)84 (17.3)0.59 (0.40-0.87)101 (22.3)42 (21.3)0.70 (0.44-1.11)
A/A10 (2.2)8 (1.6)0.38 (0.14-1.08)9 (2.0)4 (2.0)1.06 (0.27-4.25)
DominantG/G351 (77.1)394 (81.1)10.0024343 (75.7)151 (76.7)10.15
A/G-A/A104 (22.9)92 (18.9)0.56 (0.39-0.82)110 (24.3)46 (23.4)0.72 (0.46-1.13)
RecessiveG/G-A/G445 (97.8)478 (98.3)10.11444 (98.0)193 (98.0)10.84
A/A10 (2.2)8 (1.6)0.43 (0.15-1.21)9 (2.0)4 (2.0)1.15 (0.29-4.57)
Over-dominantG/G-A/A361 (79.3)402 (82.7)10.01352 (77.7)155 (78.7)10.12
A/G94 (20.7)84 (17.3)0.61 (0.41-0.89)101 (22.3)42 (21.3)0.70 (0.44-1.11)
Log-additive---0.60 (0.43-0.83)0.0018--0.78 (0.52-1.16)0.22

A comparison was made between patients with HTN and those with HTN + T2DM to analyze the correlation between the LEPR polymorphism and the occurrence of these disorders in Mongolian and Han populations. OR (95% confidence interval) (adjusted for sex and age) for Han subjects for the same five genetic models were: Co-dominant (A/G): 0.65 (0.46-0.92); co-dominant (A/A): 1.61 (0.41-6.28); dominant (A/G-A/A): 0.68 (0.49-0.96); recessive (A/A): 1.77 (0.46-6.87); over-dominant (A/G): 0.65 (0.46-0.91); and log-additive: 0.75 (0.55-1.02). All values were non-significant. For Mongolian subjects, OR (adjusted for sex and age) were: Co-dominant (A/G): 0.54 (0.36-0.81); co-dominant (A/A): 0.55 (0.17-1.79); dominant (A/G-A/A): 0.54 (0.36-0.80); recessive (A/A): 0.65 (0.20-2.11); over-dominant (A/G): 0.55 (0.37-0.82); and log-additive: 0.59 (0.41-0.84). The co-dominant A/G model, dominant A/G-A/A model, over-dominant A/G model and log-additive model were all associated with a significantly decreased risk of HTN + T2DM in Mongolian and Han patients (Table 7).

Table 7 Association of rs1137101 with hypertension and type 2 diabetes mellitus (hypertension and hypertension + type 2 diabetes mellitus).
ModelGenotypeHan, n = 892
Mongolian, n = 852
Control, n (%)
HTN with T2DM, n (%)
OR (95%CI)
P value
Control, n (%)
HTN with T2DM, n (%)
OR (95%CI)
P value
Co-dominantG/G312 (76.8)394 (81.1)10.034436 (66.6)151 (76.7)10.0067
A/G91 (22.4)84 (17.3)0.65 (0.46-0.92)202 (30.8)42 (21.3)0.54 (0.36-0.81)
A/A3 (0.7)8 (1.6)1.61 (0.41-6.28)17 (2.6)4 (2.0)0.55 (0.17-1.79)
DominantG/G312 (76.8)394 (81.1)10.026436 (66.6)151 (76.7)10.0016
A/G-A/A94 (23.1)92 (18.9)0.68 (0.49-0.96)219 (33.4)46 (23.4)0.54 (0.36-0.80)
RecessiveG/G-A/G403 (99.3)478 (98.3)10.39638 (97.4)193 (98.0)10.46
A/A3 (0.7)8 (1.6)1.77 (0.46-6.87)17 (2.6)4 (2.0)0.65 (0.20-2.11)
Over-dominantG/G-A/A315 (77.6)402 (82.7)10.012453 (69.2)155 (78.7)10.0028
A/G91 (22.4)84 (17.3)0.65 (0.46-0.91)202 (30.8)42 (21.3)0.55 (0.37-0.82)
Log-additive---0.75 (0.55-1.02)0.067--0.59 (0.41-0.84)0.0024
DISCUSSION

HTN and T2DM are major risk factors for cardiovascular and cerebrovascular diseases, and both conditions are known to result from interactions between genetics and environment[26,27]. The LEPR gene has been widely studied with respect to T2DM and HTN. We have previously demonstrated an association between rs1137101 and HTN in Han subjects and an association between rs7555955 and HTN in Mongolian subjects[28]. No association was found between rs1137101 and HTN or other metabolic traits in Mexican children[29] nor with HTN or cardiovascular disease in Iranian subjects[17]. A meta-analysis did show an association between rs1137101 and T2DM[30], and a Brazilian study suggested a relationship between T2DM and being overweight[31]. Furthermore, rs1137101 was correlated with T2DM, insulin change and being overweight among the Punjabi population of North India[32]. These findings indicate that associations are very dependent on the origins of the population under study. Inner Mongolia is a vast territory with demarcation of urban, agricultural, pastoral and part-farming/part-pastoral areas. Each region has a unique lifestyle with specific eating habits, all of which have an impact on rates of HTN. Overlain on these variations are traditional risk factors, such as smoking, drinking and salt intake[33,34] plus environmental factors[35,36]. Results of the current study were not in accord with those of previous studies and discrepancies may be due to population and lifestyle differences.

The current study focused on the conditions of HTN and HTN + T2DM in ethnic Han and Mongolian populations in Inner Mongolia. There was a significant association between rs1137101 and HTN and HTN + T2DM in Han Chinese subjects. The genotypes, AA and GA, may decrease risk of HTN and HTN + T2DM for control and HTN groups. Whereas rs1137101 was associated with a significantly increased risk of HTN for control subjects, it was associated with a decreased risk of developing T2DM for HTN patients. Further investigations involving larger study populations with further data relating to environmental and lifestyle factors are required to substantiate interactions between genetics and the environment.

CONCLUSION

The current study investigated the impact of the polymorphism rs1137101 on HTN in Mongolian subjects. Mongolian and Han subjects with HTN who had rs1137101 were protected against the development of T2DM, and rs1137101 decreased the risk of HTN and HTN + T2DM for the Han Chinese population of Inner Mongolia. In contrast with its protective role in the Han population, rs1137101 increased the risk of HTN for the Mongolian population.

ARTICLE HIGHLIGHTS
Research background

Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are each considered a risk factor for the other. Both occur frequently in the Inner Mongolia region of China. rs1137101 is a potential risk factor for the occurrence of HTN and T2DM but the association between rs1137101 and HTN + T2DM in the Mongolian and Han population in Inner Mongolia remains unknown.

Research motivation

The association between rs1137101 and occurrence of HTN + T2DM has not been fully elucidated for Mongolian and Han populations in the Inner Mongolia region.

Research objectives

To investigate the relationship between rs1137101 and the occurrence of HTN with T2DM in Mongolian and Han populations in Inner Mongolia. To illuminate the association between the rs1137101 polymorphism and HTN with T2DM by analyzing differences between Han and Mongolian Chinese.

Research methods

Data relating to blood samples, blood pressure, weight, height and other body indices among Chinese populations in Inner Mongolia. The rs1137101 polymorphism was measured. Data was analyzed by SPSS 22.0 and SNPstats software (https://www.snpstats.net/start.htm) to correlate rs1137101 with HTN + T2DM in Mongolian and Han populations in Inner Mongolia.

Research results

The association between the rs1137101 polymorphism and HTN with T2DM was analyzed, and differences between Han and Mongolian individuals were assessed. There was a significant correlation between rs1137101 with both HTN after adjustment for sex and age in individuals of Mongolian origin. rs1137101 was significantly associated with HTN and HTN + T2DM in the Han Chinese population.

Research conclusions

There was significant correlation between rs1137101 and control and HTN/HTN + T2DM in Han and Mongolian subjects. Mongolian and Han subjects with HTN who had rs1137101 were protected against the development of T2DM. rs1137101 decreased the risk of HTN and HTN + T2DM for the Han Chinese population of Inner Mongolia. By contrast, rs1137101 increased the risk of HTN for the Mongolian population.

Research perspectives

The current study analyzed the association between rs1137101 and HTN/HTN + T2DM by comparing control, HTN and HTN + T2DM groups and found rs1137101 to be associated with HTN and HTN + T2DM in Mongolian and Han populations in Inner Mongolia. Further investigations involving larger study populations with further data relating to environmental and lifestyle factors are required to substantiate interactions between genetics and the environment.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Endocrinology and metabolism

Country/Territory of origin: China

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C

Grade D (Fair): D

Grade E (Poor): 0

P-Reviewer: Javor E, Croatia; Mahmoud MZ, Saudi Arabia; Mrzljak A, Croatia S-Editor: Fan JR L-Editor: Filipodia P-Editor: Fan JR

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