PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease

Table 1 Clinical and demographic characteristics of nonalcoholic fatty liver disease patients and controls

Variables	NAFLD, n = 148	Controls, n = 137	P value
Female	111 (75.0%)	97 (70.8%)	0.426
Age (yr)	57 (46.3-63)	55 (43 61.5)	0.610
BMI (kg/m2)	32.8 ± 4.8	25.4 ± 3.3	< 0.0001
Hypertension	98 (66.2%)	24 (17.5%)	< 0.0001
Diabetes mellitus	69 (46.6%)	12 (8.8%)	< 0.0001
Dyslipidemia	108 (73.0%)	19 (13.5%)	< 0.0001
Fasting glucose (mg/dL)	101 (90-124.8)	88 (83-98)	< 0.0001
AST (U/L)	34 (25.5-56.5)	24 (20.3-29)	< 0.0001
ALT (U/L)	38 (28-70.5)	29.5 (23-38)	< 0.0001
GGT (U/L)	53 (29-116)	28 (18.5-55.5)	< 0.0001
ALP (U/L)	97 (74-116.8)	75 (58.3-83.8)	< 0.0001
Total bilirubin (mg/dL)	0.6 (0.5-0.9)	0.7 (0.5-0.8)	0.438
Triglycerides (mg/dL)	162.5 (110-205.3)	126.5 (93-176)	0.006
Total cholesterol (mg/dL)	195.8 ± 41.5	179.9 ± 47.1	0.006
VLDL (mg/dL)	32 (22-42.3)	24.5 (17.3-33.8)	0.001
HDL (mg/dL)	48 (39.5-54)	47 (40.5-60.8)	0.404
LDL (mg/dL)	107.5 (89.5-137.9)	96 (67.8-117.5)	0.009
Platelets (109/L)	219.4 ± 81.8	254.6 ± 82.4	0.439
Ferritin (ng/mL)	89 (42.7-168.5)	32 (32-32)	0.349
D vitamin (ng/mL)	22 (19-27.7)	26.95 (20.5-32.5)	0.139

The data are expressed as n (%), or as mean ± SD for normally distributed variables and as median (interquartile range) when distribution of the variable was skewed. NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; AST: Serum aspartate aminotransferase; VLDL: Very low-density lipoprotein; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; LDL: Low-density lipoprotein cholesterol.

Table 2 Clinical and demographic characteristics of the nonalcoholic steatohepatitis and simple steatosis population

Variables	NASH, n = 54	Simple steatosis, n = 94	P value
Female	44 (81.5%)	67 (71.3%)	0.169
Age (yr)	59 (45.8-63)	57 (47.8-64)	0.935
BMI (kg/m2)	32.7 ± 4.8	32.8 ± 4.8	0.968
WC	106.6 (100-114)	105.3 (96-113.8)	0.306
Arterial hypertension	39 (72.2%)	59 (62.8%)	0.886
Diabetes mellitus	35 (64.8%)	34 (36.2%)	0.007
Dyslipidemia	45 (83.3%)	63 (67.0%)	0.248
Fasting insulin	16.5 (11.9-31)	14 (8-18)	0.055
Fasting glucose (mg/dL)	112.5 (91-151.5)	98 (90-112)	0.019
AST (U/L)	53.5 (31.7-69)	30 (23-38)	< 0.001
ALT (U/L)	61 (36-79.3)	33 (24-49)	< 0.001
GGT (U/L)	87 (51.7-164.3)	39 (27-73.3)	< 0.001
ALP (U/L)	99 (78-127.5)	88 (72-116)	0.075
Total bilirubin (mg/dL)	0.59 (0.5-0.9)	0.6 (0.5-0.9)	0.986
Triglycerides (mg/dL)	162 (113-227.8)	163 (109.25-201)	0.544
Total cholesterol (mg/dL)	196.4 ± 39.9	195.4 ± 42.7	0.793
VLDL (mg/dL)	32 (22.8-45.3)	32 (22-40.8)	0.440
HDL (mg/dL)	46 (37.8-53)	48 (40-55)	0.432
LDL (mg/dL)	108.5 (89-138.4)	107 (88.5-137.4)	0.793
Platelets (109/L)	184 ± 67.4	308 ± 1.4	0.053
Ferritin (ng/mL)	109 (56.75-267.5)	69 (37.2-143.8)	0.019
D vitamin (ng/mL)	21.1 (17.55-25.9)	23.4 (19-28)	0.086
HOMA-IR	5.26 (2.97-8.8)	3.36 (1.77-4.7)	0.330

The data are expressed as n (%), or as mean ± SD for normally distributed variables and as median (interquartile range) when distribution of the variable was skewed. NASH: Nonalcoholic steatohepatitis; BMI: Body mass index; AST: Serum aspartate aminotransferase; VLDL: Very low-density lipoprotein; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; LDL: Low-density lipoprotein cholesterol.

Table 3 PNPLA3 rs738409 genotype frequencies in nonalcoholic fatty liver disease patients and controls

	Genotype frequency % (n)			P value
	CC	CG	GG
NAFLD	37.2 (55)	43.9 (65)	18.9 (28)	< 0.001
Controls	58.4 (80)	31.4 (43)	10.2 (14)

Data were analyzed by the Chi-square test. NAFLD: Nonalcoholic fatty liver disease.

Table 4 Association between the PNPLA3 rs738409 genotype and nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, adjusted for age, gender, body mass index and diabetes

Genotypes	OR	95%CI	P value
NAFLD vs Control
CC vs CG/GG	1.69	1.21–2.36	0.002
CC vs GG	3.13	1.49–6.57	0.003
NASH vs SS
CC vs CG/GG	3.50	1.84–6.64	< 0.001
CC vs GG	5.53	2.04-14.92	0.001

NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.

Table 5 Association of the PNPLA3 rs738409 genotype and activity of nonalcoholic steatohepatitis and fibrosis, adjusted for age, gender, body mass index and diabetes, evaluated by multivariate binary logistic regression analysis

Genotypes	OR	95%CI	P value
Activity of NASH (A > 2 vs A < 2)
CC vs CG/GG	0.65	0.22-1.88	0.433
CC vs GG	17.11	1.87 - 156.25	0.012
Fibrosis (presence vs absence)
CC vs CG/GG	3.05	1.01-9.17	0.046
CC vs GG	7.42	1.55-35.47	0.012

NASH: Nonalcoholic steatohepatitis.

Table 6 TM6SF2 rs58542926 genotype frequencies in nonalcoholic fatty liver disease patients and controls

	Genotype frequency % (n)			P value
	CC	CT	TT
NAFLD	83.2 (125)	14.9 (22)	0.7 (1)	0.78
Controls	84.5 (114)	16.1 (22)	0.7 (1)

NAFLD: Nonalcoholic fatty liver disease.