Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

doi:10.3748/wjg.v21.i28.8605

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Jul 28, 2015 (publication date) through Apr 23, 2024

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World Journal of Gastroenterology

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World J Gastroenterol. Jul 28, 2015; 21(28): 8605-8614
Published online Jul 28, 2015. doi: 10.3748/wjg.v21.i28.8605

Table 1 Demographic and clinical data of all patients

Variable	Normal group (n = 47)	CHB group (n = 51)	CHB + NAFLD group (n = 57)	P value
Age (yr)	46.74 ± 6.97	36.76 ± 12.60	38.98 ± 13.55	< 0.001
Sex, n (%)	M: 29 (61.70)	M: 34 (66.67)	M: 42 (73.68)	0.420
Sex, n (%)	F: 18 (38.30)	F: 17 (33.33)	F: 15 (26.32)	0.420
BMI (kg/m²)	23.43 ± 2.59	22.84 ± 2.97	27.40 ± 3.24	< 0.001
TC (mmol/L)	4.40 ± 1.22	4.39 ± 0.96	4.89 ± 0.84	0.023
TG (mmol/L)	0.98 ± 0.31	1.12 ± 0.38	1.84 ± 1.35	< 0.001
HDL (mmol/L)	1.51 ± 1.22	1.50 ± 0.44	1.20 ± 0.28	0.142
LDL (mmol/L)	2.03 ± 0.85	2.22 ± 0.56	2.94 ± 1.02	< 0.001
FBG (mmol/L)	3.39 ± 1.30	4.11 ± 0.63	5.71 ± 1.92	< 0.001
ALT (U/L)	13. 72 ± 4.16	76.14 ± 53.70	68.51 ± 47.20	< 0.001
TBIL (μmol/L)	2.25 ± 0.51	23.78 ± 21.44	5.80 ± 3.55	< 0.001
GGT (U/L)	16.42 ± 7.31	94.33 ± 94.13	60.18 ± 36.81	< 0.001
ALP (U/L)	16.08 ± 5.48	95.23 ± 40.35	101.16 ± 88.46	< 0.001

CHB: Chronic hepatitis B; NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; TC: Total cholesterol; TG: Triglyceride; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; FBG: Fasting blood glucose; ALT: Alanine aminotransferase; TBIL: Total bilirubin; GGT: γ-glutamyltransferase; ALP: Alkaline phosphatase.

Table 2 Association tests of PNPLA3 single nucleotide polymorphisms

Groups	SNPs	Group (%)			OR (95%CI)			P value
Groups	SNPs	Normal	CHB	CHB + NAFLD	Unadjusted	Adjusted for age, sex	Adjusted for age, sex, and BMI	Unadjusted	Adjusted for age and sex	Adjusted for age, sex, and BMI
CHB+NAFLD vs CHB	738409		C: 57.84G: 42.16	C: 44.74G: 55.26	1.695(0.989-2.906)	2.334(1.169-4.657)	2.774(1.176-6.543)	0.054	0.016	0.020
	3747206		C: 57.84T: 42.16	C: 44.74T: 55.26	1.695(0.989-2.906)	2.334(1.169-4.657)	2.774(1.176-6.543)	0.054	0.016	0.020
	4823173		G: 58.82A: 41.18	G: 45.61A: 54.39	1.703(0.993-2.922)	2.134(1.089-4.180)	2.734(1.161-6.437)	0.052	0.027	0.021
	2072906		A: 58.82G: 41.18	C: 44.74G: 55.26	1.765 (1.028-3.029)	2.314(1.174-4.559)	3.045(1.277-7.262)	0.039	0.015	0.012
CHB+NAFLD vs normal	738409	C: 63.83G: 36.17		C: 44.74G: 55.26	2.180(1.246-3.815)	2.529(1.335-4.792)	3.018(1.318-6.914)	0.00	0.004	0.009
	3747206	C: 63.83G: 36.17		C: 44.74T: 55.26	2.180(1.246-3.815)	2.529(1.335-4.792)	3.018(1.318-6.914)	0.006	0.004	0.009
	4823173	C: 63.83G: 36.17		G: 45.61A: 54.39	2.104(1.203-3.681)	2.536(1.329-4.840)	3.212(1.344-7.679)	0.009	0.005	0.009
	2072906	C: 63.83G: 36.17		C: 44.74G: 55.26	2.180(1.246-3.815)	2.684(1.403-5.134)	3.499(1.452-8.430)	0.006	0.003	0.005
CHB vs normal	738409	C: 63.83G: 36.17	C: 57.84G: 42.16		1.286( 0.723-2.287)	1.356(0.695-2.643)	1.315(0.674-2.567)	0.391	0.372	0.422
	3747206	C: 63.83G: 36.17	C: 57.84T: 42.16		1.286(0.723-2.287)	1.356(0.695-2.643)	1.315(0.674-2.567)	0.391	0.372	0.422
	4823173	C: 63.83G: 36.17	G: 58.82A: 41.18		1.235(0.694-2.199)	1.439(0.717-2.889)	1.325(0.652-2.694)	0.472	0.306	0.437
	2072906	C: 63.83G: 36.17	G: 58.82A: 41.18		1.235(0.694-2.199)	1.439(0.717-2.889)	1.325(0.652-2.694)	0.472	0.306	0.437

BMI: Body mass index; CHB: Chronic hepatitis B; CI: Confidence interval; NAFLD: Nonalcoholic fatty liver disease; OR: Odds ratio; SNPs: Single nucleotide polymorphisms.

Table 3 Association tests of PNPLA3 single nucleotide polymorphisms with histological features in chronic hepatitis B + nonalcoholic fatty liver disease patients

Condition	PNPLA3 genotype			P value
Condition	CC (n = 12)	CG (n = 27)	GG (n = 18)	P value
Steatosis	rs738409: CC	rs738409: CG	rs738409: GG	rs738409: 0.384;
	M: ≤ 1: 5 (41.67%);	M: ≤ 1: 11 (40.74%);	M: ≤ 1: 4 (22.22%);	rs3747206: 0.384;
	F: > 1: 7 (58.33%)	F: > 1: 16 (59.26%)	F: > 1: 14 (77.73%)	rs4823173: 0.374;
	rs3747206: CC	rs3747206: CT	rs3747206: TT	rs2072906: 0.275
	M: ≤ 1: 5 (41.67%);	M: ≤ 1: 11 (40.74%);	M: ≤ 1: 4 (22.22%);
	F: > 1: 7 (58.33%)	F: > 1: 16 (59.26%)	F: > 1: 14 (77.73%)
	rs4823173: GG	rs4823173: GA	rs4823173: AA
	M: ≤ 1: 5 (38.46%);	M: ≤ 1: 11 (42.31%);	M: ≤ 1: 4 (22.22%);
	F: > 1: 8 (61.54%)	F: > 1: 15 (57.69%)	F: > 1: 14 (77.73%)
	rs2072906: AA	rs2072906: AG	rs2072906: GG
	M: ≤ 1: 5 (38.46%);	M: ≤ 1: 11 (44.00%);	M: ≤ 1: 4 (21.05%);
	F: >1: 8 (61.54%)	F: > 1: 14 (56.00%)	F: > 1: 15 (78.95%)
Lobular inflammation	rs738409: CC	rs738409: CG	rs738409: GG	rs738409: 0.706;
	M: ≤ 1: 5 (41.67%);	M: ≤ 1: 10 (37.04%);	M: ≤ 1: 5 (27.78%);	rs3747206: 0.706;
	F: > 1: 7 (58.33%)	F: > 1: 17 (62.96%)	F: > 1: 13 (72.22%)	rs4823173: 0.570;
	rs3747206: CC	rs3747206: CT	rs3747206: TT	rs2072906: 0.509
	M: ≤ 1: 5 (41.67%);	M: ≤ 1: 10 (37.04%);	M: ≤ 1: 5 (27.78%);
	F: > 1: 7 (58.33%)	F: > 1: 17 (62.96%)	F: > 1: 13 (72.22%)
	rs4823173: GG	rs4823173: GA	rs4823173: AA
	M: ≤ 1: 6 (46.15%);	M: ≤ 1: 9 (34.62%);	M: ≤ 1: 5 (27.78%);
	F: > 1: 7 (53.85%)	F: > 1: 17 (65.38%)	F: > 1: 13 (72.22%)
	rs2072906: AA	rs2072906: AG	rs2072906: GG
	M: ≤ 1: 6 (46.15%);	M: ≤ 1: 9 (36.00%);	M: ≤ 1: 5 (26.32%);
	F: > 1: 7 (53.85%)	F: > 1: 16 (64.00%)	F: > 1: 14 (73.68%)
Ballooning	rs738409: CC	rs738409: CG	rs738409: GG	rs738409: 0.021
	M: ≤ 1: 6 (50.0%);	M: ≤ 1: 9 (33.33%);	M: ≤ 1: 1 (5.56%);	(CC vs GG: P = 0.005; CG vs GG: P = 0.028);
	F: > 1: 6 (50.0%)	F: > 1: 18 (66.67%)	F: > 1: 17 (94.44%)	rs3747206: 0.021
	rs3747206: CC	rs3747206: CT	rs3747206: TT	(CC vs TT: P = 0.005; CT vs TT: P = 0.028);
	M: ≤ 1: 6 (50.00%);	M: ≤ 1: 9 (33.33%);	M: ≤ 1: 1 (5.56%);	rs4823173: 0.012
	F: > 1: 6 (50.00%)	F: > 1: 18 (66.67%)	F: > 1: 17 (94.44%)	(GG vs AA: P = 0.002; GA vs AA: P = 0.041);
	rs4823173: GG	rs4823173: GA	rs4823173: AA	rs2072906: 0.009
	M: ≤ 1: 7 (53.85%);	M: ≤ 1: 8 (30.77%);	M: ≤ 1: 1 (5.56%);	(AA vs GG: P = 0.002; AG vs GG: P = 0.029)
	F: > 1: 6 (46.15%)	F: > 1: 18 (69.23%)	F: > 1: 17 (94.44%)
	rs2072906: AA	rs2072906: AG	rs2072906: GG
	M: ≤ 1: 7 (53.85%);	M: ≤ 1: 8 (32.0%);	M: ≤ 1: 1 (5.26%);
	F: > 1: 6 (46.15%)	F: > 1: 17 (68.0%)	F: > 1: 18 (94.74%)
NAS	rs738409: CC	rs738409: CG	rs738409: GG	rs738409: 0.039
	M: < 3: 10 (83.33%);	M: < 3: 11 (40.74%);	M: < 3: 8 (44.44%);	(CC vs CG: P = 0.014; CC vs GG: P = 0.033);
	F: ≥ 3: 2 (16.67%)	F: ≥ 3: 16 (59.26%)	F: ≥ 3: 10 (55.56%)	rs3747206: 0.039
	rs3747206: CC	rs3747206: CT	rs3747206: TT	(CC vs CG: P = 0.014; CC vs GG: P = 0.033);
	M: < 3: 10 (83.33%);	M: < 3: 11 (40.74%);	M: < 3: 8 (44.44%);	rs4823173: 0.020
	F: ≥ 3: 2 (16.67%)	F: ≥ 3: 16 (59.26%)	F: ≥ 3: 10 (55.56%)	(GG vs GA: P = 0.006; GG vs AA: P = 0.023);
	rs4823173: GG	rs4823173: GA	rs4823173: AA	rs2072906: 0.021
	M: < 3: 11 (84.62%);	M: < 3: 10 (38.46%);	M: < 3: 8 (44.44%);	(AA vs AG: P = 0.009; AA vs GG: P = 0.016)
	F: ≥ 3: 2 (15.38%)	F: ≥ 3: 16 (61.54%)	F: ≥ 3: 10 (55.56%)
	rs2072906: AA	rs2072906: AG	rs2072906: GG
	M: < 3: 11 (84.62%);	M: < 3: 10 (40.0%);	M: < 3: 8 (42.11%);
	F: ≥ 3: 2 (15.38%)	F: ≥ 3: 15 (60.0%)	F: ≥3: 11 (57.89%)
Fibrosis grading	rs738409: CC	rs738409: CG	rs738409: GG	rs738409: 0.032
	M: ≤ 1: 11 (91.67%);	M: ≤ 1: 17 (62.96%);	M: ≤ 1: 8 (44.44%);	(CC vs GG: P = 0.009);
	F: > 1: 1 (8.33%)	F: > 1: 10 (37.04%)	F: > 1: 10 (55.56%)	rs3747206: 0.032
	rs3747206: CC	rs3747206: CT	rs3747206: TT	(CC vs TT: P= 0.009);
	M: ≤ 1: 11 (91.67%);	M: ≤ 1: 17 (62.96%);	M: ≤ 1: 8 (44.44%);	rs4823173: 0.024
	F: > 1: 1 (8.33%)	F: > 1: 10 (37.04%)	F: > 1: 10 (55.56%)	(GG vs GA: P = 0.044; GG vs AA: P = 0.006);
	rs4823173: GG	rs4823173: GA	rs4823173: AA	rs2072906: 0.015
	M: ≤ 1: 12 (92.31%);	M: ≤ 1: 16 (61.54%);	M: ≤ 1: 8 (44.44%);	(AA vs GG: P = 0.004)
	F: > 1: 1 (7.69%)	F: > 1: 10 (38.46%)	F: > 1: 10 (55.56%)
	rs2072906: AA	rs2072906: AG	rs2072906: GG
	M: ≤ 1: 12 (92.31%);	M: ≤ 1: 16 (64.0%);	M: ≤ 1: 8 (42.11%);
	F: > 1: 1 (7.69%)	F: > 1: 9 (36.0%)	F: > 1: 11 (57.89%)

NAS: Nonalcoholic fatty liver disease activity score.

Citation: Pan Q, Zhang RN, Wang YQ, Zheng RD, Mi YQ, Liu WB, Shen F, Chen GY, Lu JF, Zhu CY, Zhang SY, Chen YM, Sun WL, Fan JG. Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B. World J Gastroenterol 2015; 21(28): 8605-8614
URL: https://www.wjgnet.com/1007-9327/full/v21/i28/8605.htm
DOI: https://dx.doi.org/10.3748/wjg.v21.i28.8605