Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

doi:10.4254/wjh.v16.i3.366

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 16, Issue 3

This Article

Academic Content and Language Evaluation of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Supplementary Materials of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (3131)

All Articles published online

The chart showing PDF series, HTML series, Figures (1-1) series, Tables (1-7) series.

Item

Count

PDF

HTML

1395

Figures (1-1)

186

Tables (1-7)

149

Sum=1797

Featured Article

The chart showing Browse series, Download series.

Item

Count

Browse

268

Download

565

Sum=833

Publishing Process of This Article

Item

Count

Browse

Download

359

Sum=420

Mar 27, 2024 (publication date) through Dec 24, 2024

Times Cited of This Article

Times Cited (0)

Journal Information of This Article

Publication Name

World Journal of Hepatology

ISSN

1948-5182

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Case Control Study

World J Hepatol. Mar 27, 2024; 16(3): 366-378
Published online Mar 27, 2024. doi: 10.4254/wjh.v16.i3.366

Table 1 Baseline characteristics of metabolic-associated fatty liver disease patients and controls

Characteristics	PLWH and MAFLD (n = 83)	PLWH and non-MAFLD (n = 94)	P value	MAFLD (n = 145)	P value	Chinese Dai (n = 93)	P value
Age (yr)	51.99 ± 7.65	49.55 ± 8.27	0.044^a	65.00	< 0.001^b	N/A	N/A
Gender
Male	54 (65.10)	48 (51.10%)	0.060	68 (46.90%)	0.008^b	44 (47.30%)	0.950
Female	48 (34.90%)	46 (48.90%)		77 (53.10%)		49 (52.70%)
BMI (kg/m²)	25.42	21.79	< 0.001^a	27.67	< 0.001^b	N/A	-
CD4 (cells/mm³)	619.00	570.50	0.033^a	N/A	-	N/A	-
%CD 4	26.10 ± 0.83	25.76 ± 0.81	0.853	N/A	-	N/A	-
Hb (g/dL)	14.36 1.62	13.84 1.90	0.015^a	N/A		N/A
Platelets (-/mm³)	259063 77332	261694 66966	0.744	N/A		N/A
AP (U/L)	85.00	86.00	0.821	72.00	0.001^b	N/A	-
AST (U/L)	33.00	28.00	< 0.001^a	38.00	0.015^b	N/A	-
ALT (U/L)	38.00	25.00	< 0.001^a	50.00	0.004^b	N/A	-
GGT (U/L)	47.00	35.50	< 0.001^a	51.50	0.853	N/A	-
Total protein (g/L)	79.60 ± 0.56	78.28 ± 0.47	0.071	75.96 ± 0.42	< 0.001^b	N/A	-
Albumin (g/L)	40.80	38.35	< 0.001^a	40.65	0.255	N/A	-
Total bilirubin (mg/dL)	0.60	0.50	0.759	0.70	0.10	N/A	-
Direct bilirubin (mg/dL)	0.20	0.20	0.862	0.30	0.007^b	N/A	-
HbA1C (mmol/L)	5.68	5.38	< 0.001^a	6.36	< 0.001^b	N/A	-
Fasting plasma Glucose (mg/dL)	98	93	0.026	108	< 0.001^b	N/A	-
Triglyceride (mg/dL)	169	109	< 0.001^a	123	< 0.0001^b	N/A	-
Total Cholesterol (mg/dL)	206.78 ± 5.57	199.10 ± 3.57	0.212	183	0.428	N/A	-
HDL (mg/dL)	44	49	0.004^a	49	0.10	N/A	-
LDL (mg/dL)	130.67 ± 4.27	122.46 ± 2.98	0.086	114.94 ± 2.83	0.001^b	N/A	-
Drug-regimen, n (%)
NRTI+NNRTI	62 (74.7)	71 (75.5)	0.573	N/A	-	N/A	-
NRTI+PI	19 (22.9)	18 (19.1)		N/A	-	N/A	-
Alternative	2 (2.4)	5 (5.3)		N/A	-	N/A	-
Co-morbidities
Dyslipidemia	30 (36.1)	15 (16.0)	0.002^a	82 (56.9)	0.002^b	N/A	-
Hypertension	21 (25.3)	6 (6.4)	0.001^a	64 (44.1)	0.003^b	N/A	-
Diabetes mellitus	16 (19.3)	5 (5.3)	0.005^a	63 (43.4)	< 0.001^b	N/A	-

^aP value < 0.05 compared between people living with human immunodeficiency virus (PLWH) and metabolic-associated fatty liver disease (MAFLD) vs PLWH and non-MAFLD.

^bP value < 0.05 compared between PLWH and MAFLD vs MAFLD.

Data represent as mode, mean ± standard deviation or n (%), differences between groups were tested by Chi-square test or one-way ANOVA as appropriate. AP: Alkaline phosphatase; AST: Aspartate aminotransaminase; ALT: Alanine aminotransaminase; ALP: Alkaline phosphatase; Hb: Henoglobin; TB: Total bilirubin; MAFLD: Metabolic-associated fatty liver disease; N/A: Not available; PLWH: People living with human immunodeficiency virus; GGT: Gamma-glutamyl transferase; HbA1C: Hemoglobin A1C; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; NRTI: Nucleoside reverse transcriptase inhibitor; NNRTI: Non-nucleoside reverse transcriptase inhibitor; PI: Protease inhibitor.

Table 2 Genotype distributions and Minor allele frequency of candidates single-nucleotide polymorphisms

Polymorphism	PLWH and MAFLD (n = 83)	PLWH and non-MAFLD (n = 94)	P value	MAFLD (n = 145)	Chinese Dai (n = 94)	P value
PNPLA3 rs738409
MAF = G	57 (34.33)	56 (29.78)	0.413	92 (31.73)	43 (23.12)	0.035^a
APOC3 rs2854116
MAF=T	81 (47.09)	87(46.28)	0.691	128 (44.14)	88 (47.31)	< 0.001^b
LEP rs7799039
MAF=G	57 (33.14)	57 (30.32)	0.738	85 (29.31)	48 (25.81)	0.674
GHRL rs27647
MAF = C	13 (7.56)	25 (13.30)	0.055	28 (9.66)	18 (9.68)	0.702
LIPC rs1800588
MAF = T	70 (42.17)	70 (37.33)	0.421	101 (34.83)	67 (36.02)	0.872
APOB rs10495712
MAF = A	15 (8.06)	14 (7.45)	0.853	22 (7.59)	8 (4.30)	0.339
APOA5 rs662799
MAF = G	41 (22.04)	51 (27.13)	0.766	75 (25.86)	52 (27.96)	0.834

^aP value < 0.05 compared between people living with human immunodeficiency virus (PLWH) and metabolic-associated fatty liver disease (MAFLD) vs PLWH and non-MAFLD.

^bP value < 0.05 compared between PLWH and MAFLD vs MAFLD MAF minor allele frequency, Chinese Dai was represented as general population. Data represented as n (%), PLWH and MAFLD vs other groups, differences between groups were tested by Chi-square test. MAFLD: Metabolic-associated fatty liver disease; PLWH: People living with human immunodeficiency virus; MAF: Metabolic-associated fatty.

Table 3 Genotype and allele frequencies of the single-nucleotide polymorphisms in the people living with human immunodeficiency virus and metabolic-associated fatty liver disease compared with people living with human immunodeficiency virus and non-metabolic-associated fatty liver disease group

Gene	SNP	B allele	Dominant model				Recessive model
			PLWH and MAFLD vs PLWH and non-MAFLD		PLWH and MAFLD vs Chinese Dai		PLWH and MAFLD vs PLWH and non-MAFLD		PLWH and MAFLD vs Chinese Dai
			OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
PNPLA3	rs738409	G	1.476 (0.809-2.694)	0.204	2.539 (1.382-4.665)	0.002^b	0.94 (0.276-3.202)	0.921	0.929 (0.273-3.166)	0.907
APOC3	rs2854116	C	1.117 (0.543-2.297)	0.764	1.203 (0.588-2.462)	0.613	0.798 (0.411-1.550)	0.506	0.828 (0.425-1.614)	0.579
LEP	rs7799039	G	0.704 (0.287-1.727)	0.422	0.408 (0.146-1.142)	0.080	0.886 (0.491-1.601)	0.689	0.730 (0.403-1.322)	0.298
GHRL	rs27647	G	0.466 (0.217-1.001)	0.047^a	0.704 (0.317-1.566)	0.388	2.146 (1.832-2.514)	0.469	2.134 (1.823-2.499)	0.472
LIPC	rs1800588	T	1.506 (0.806-2.815)	0.198	1.676 (0.898-3.128)	0.104	1.053 0.452-2.456)	0.905	1.040 (0.446-2.427)	0.928
APOB	rs10495712	A	1.264 (0.557-2.871)	0.575	2.156 (0.855-5.436)	0.098	1.134 (0.070-18.422)	1.000	2.134 (1.823-2.499)	0.472
APOA5	rs662799	G	0.914 (0.505-1.654)	0.766	0.960 (0.330-2.790)	0.940	0.629 (0.177-2.231)	0.470	0.734 (0.200-2.697)	0.751

Data expressed as OR odds ratio, CI confidence interval.

^aP value < 0.05 compared between people living with human immunodeficiency virus (PLWH) and metabolic-associated fatty liver disease (MAFLD) vs PLWH and non-MAFLD.

^bP value < 0.05 compared between PLWH and MAFLD vs Chinese Dai was represented as general population, B-allele expressed risk allele. MAFLD: Metabolic-associated fatty liver disease; PLWH: People living with human immunodeficiency virus; SNP: Single-nucleotide polymorphism.

Table 4 Genotype and allele frequencies of the single-nucleotide polymorphisms in the metabolic-associated fatty liver disease compared with Chinese Dai

Gene	SNP	B allele	Dominate model		Recessive model
Gene	SNP	B allele	OR (95%CI)	P value	OR (95%CI)	P value
PNPLA3	rs738409	G	1.970 (1.160-3.345)	0.012^a	1.074 (0.377-3.061)	0.894
APOC3	rs2854116	C	6.109 (2.490-14.986)	< 0.001^a	0.485 (0.259-0.907)	0.022^b
LEP	rs7799039	G	0.840 (0.300-2.355)	0.740	0.790 (0.469-1.332)	0.376
GHRL	rs27647	G	0.953 (0.491-1.850)	0.888	1.646 (1.486-1.823)	1.000
LIPC	rs1800588	T	0.889 (0.525-1.504)	0.661	1.042 (0.494-2.199)	0.914
APOB	rs10495712	A	1.799 (0.762-4.251)	0.176	1.642 (1.486-1.823)	1.000
APOA5	rs662799	G	0.854 (0.507-1.438)	0.552	0.960 (0.330-2.790)	0.940

^aP value < 0.05 compared between metabolic-associated fatty liver disease (MAFLD) vs Chinese Dai in dominant model.

^bP value < 0.05 compared between MAFLD vs Chinese Dai in recessive model, B-allele expressed risk allele. Data expressed as n (%). MAFLD: Metabolic-associated fatty liver disease; PLWH: People living with human immunodeficiency virus; SNP: Single-nucleotide polymorphism; OR: Odds ratio.

Table 5 Association between genetic polymorphism and Lipid profile

Genetic polymorphisms	Lipid parameters
Genetic polymorphisms	Triglyceride (mg/dL), (n = 177)		Total cholesterol (mg/dL), (n = 177)		LDL-cholesterol (mg/dL), (n = 177)		HDL-cholesterol (mg/dL), (n = 66)	HDL-cholesterol (mg/dL), (n = 111)
	< 150	≥ 150	< 200	≥ 200	< 130	≥ 130	Men ≥ 40 mg/dL, women ≥ 50 mg/dL	Men < 40 mg/dL, women < 50 mg/dL
PNPLA3 rs738409 CC vs CG+GG
OR (95%CI)	0.699 (0.383-1.277)		1.053 (0.580-1.912)		1.088 (0.597-1.981)		0.9967 (0.538 -1.846)
P value	0.243		0.865		0.784		0.992
APOC3 rs2854116 TT vs CT+CC
OR (95%CI)	0.796 (0.387-1.635)		1.611 (0.780-3.328)		1.173 (0.568-2.423)		0.4696 (0.253-0.873)
P value	0.534		0.195		0.666		0.017^a
APOA5 rs662799 AA vs AG+GG
OR (95%CI)	1.021 (0.562-1.855)		0.543 (0.299-0.989)		0.595 (0.326-1.084)		0.739 (0.374-1.461)
P value	0.946		0.045^a		0.089		0.385
APOB rs10495712 (GG vs AG+AA)
OR (95%CI)	0.749 (0.322-1.743)		0.719 (0.315-1.639)		0.807 (0.351-1.855)		0.816 (0.343-1.938)
P value	0.501		0.431		0.613		0.645
LIPC rs1800588 CC vs CT+TT
OR (95%CI)	0.870 (0.467-1.621)		0.732 (0.393-1.363)		0.607 (0.326-1.132)		0.911 (0.482-1.722)
P value	0.661		0.325		0.115		0.774
LEP rs7799039 GG vs AG+AA
OR (95%CI)	9.316 (2.064-40.428)		1.623 (0.655-4.017)		1.518 (0.602-3.825)		1.317 (0.507-3.419)
P value	0.001^a		0.292		0.374		0.572
GHRL rs27647 (AA vs AG+GG)
OR (95%CI)	0.570 (0.265-1.224)		0.997 (0.483-2.058)		0.905 (0.436-1.878)		0.889 (0.417-1.895)
P value	0.147		0.993		0.788		0.761

^aP < 0.05 compare between normal level vs abnormal level. OR: Odds ratio; HDL: High-density lipoprotein; LDL: Low-density lipoprotein.

Table 6 Association between genetic polymorphism and metabolic traits

Genetic polymorphisms	Metabolic traits
Genetic polymorphisms	FPG (mg/dL), n = 175		HbA1C (mmol/L), n = 159		AST (U/L), n = 175		ALT (U/L), n = 177
	< 100	≥ 100	< 6.5	≥ 6.5	< 34	≥ 34	< 40	≥ 40
PNPLA3 rs738409 (CC vs CG+GG)
OR (95%CI)	0.354 (0.063-1.984)		1.055 (0.437-2.543)		2.568 (1.243-5.305)		1.679 (0.713-3.953)
P value	0.219		0.906		0.010^a		0.232
APOC3 rs2854116 (TT vs CT+CC)
OR (95%CI)	0.956 (0.923-0.991)		1.553 (0.495-4.897)		0.735 (0.335-1.614)		0.630 (0.253-1.570)
P value	0.342		0.448		0.442		0.318
APOA5 rs662799 (AA + AG+GG)
OR (95%CI)	1.167 (0.229-5.946)		1.213 (0.509-2.893)		0.823 (0.421-1.611)		0.730 (0.320-1.664)
P value	1.000		0.663		0.570		0.453
APOB rs10495712 (GG vs AG+AA)
OR (95%CI)	1.100 (0.123-9.802)		1.150 (0.356-3.720)		2.063 (0.879-4.840)		1.255 (0.431-3.651)
P value	0.923		0.815		0.092		0.774
LIPC rs1800588 (CC vs CT+TT)
OR (95%CI)	0.947 (0.907-0.989)		1.709 (0.636-4.592)		1.476 (0.719-3.027)		2.208 (0.844-5.776)
P value	0.093		0.284		0.287		0.100
LEP rs7799039 (GG vs AG+AA)
OR (95%CI)	0.268 (0.046-1.561)		1.008 (0.272-3.746)		1.329 (0.462-3.827)		2.016 (0.444-9.155)
P value	0.166		1.000		0.579		0.535
GHRL rs27647 (AA vs AG+GG)
OR (95%CI)	1.045 (1.009-1.083)		0.700 (0.222-2.206)		0.676 (0.285-1.605)		0.795 (0.280-2.256)
P value	0.345		0.541		0.373		0.666

^aP value < 0.05. AST: Aspartate aminotransaminase; ALT Alanine aminotransaminase; OR: Odds ratio; FPG: Fasting plasma glucose; HbA1C: Hemoglobin A1C.

Table 7 Logistic regression analysis of factors associated with metabolic-associated fatty liver disease (people living with human immunodeficiency virus and metabolic-associated fatty liver disease vs people living with human immunodeficiency virus and non-metabolic-associated fatty liver disease)

Factor	Exp(B)	95%CI	P value
AST	4.615	1.081-19.709	0.039^a
Fasting Plasma glucose	21.5	5.327-86.767	< 0.001^a
Triglyceride	6.747	1.747-26.047	0.006^a
Total cholesterol	0.125	0.019-0.819	0.030^a
LDL	12.97	1.983-84.827	0.007^a
APOB rs10495712	4.195	1.304-18.532	0.019^a
APOA5 rs662799	0.012	0.002-0.770	< 0.001^a
LEP rs7799039	0.321	0.070-1.469	0.143^a

^aP value < 0.2. AST: Aspartate aminotransaminase; LDL: Low-density lipoprotein.

Citation: Choochuay K, Kunhapan P, Puangpetch A, Tongsima S, Srisawasdi P, Sobhonslidsuk A, Sungkanuparph S, Biswas M, Sukasem C. Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus. World J Hepatol 2024; 16(3): 366-378
URL: https://www.wjgnet.com/1948-5182/full/v16/i3/366.htm
DOI: https://dx.doi.org/10.4254/wjh.v16.i3.366