Genetic polymorphism of IFI16 and AIM2 among Pakistani hepatitis C virus-induced fibrosis patients

Table 1 Baseline demographic, clinical, laboratory features, fibrosis stage, and IFI16 (rs1057028) and AIM2 (rs2814770) genotypic and allelic frequency in the present study population

Characteristics	CHC patients (n = 378)
Age (years)	40 (32-50)
BMI (kg/m2)	26.8 (24-30)
HCV-RNA log10 (IU/mL)	4.58 (3.75-5.41)
ALT (IU/L)	59 (41-88)
AST (IU/L)	55 (39.2-89.5)
Bilirubin (mg/dL)	0.8 (0.7-0.9)
Metavir staging
F0-F1	223 (59.5)
F2	17 (4.5)
F3	59 (15.7)
F4	76 (20.3)
IFI16 rs1057028 (n = 378)
AA	209 (55.3)
AT	100 (26.5)
TT	69 (18.3)
A	518 (69)
T	238 (31)
AIM2 rs2814770 (n = 140)
CC	41 (29.3)
CT	60 (42.9)
TT	39 (27.9)
C	142 (51)
T	138 (49)

Data were showed as n (%) or median (interquartile range). CHC: Chronic hepatitis C; BMI: Body mass index; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 2 Allele and genotype frequencies and association of IFI16 (rs1057028) polymorphism with advanced fibrosis (≥ F2), assuming different genetic models, n (%)

SNP	Model	Genotype	CHC patients		OR (95%CI)	P value	AIC
			Fibrosis grade (F0-F1), n = 223	Fibrosis grade (F2-F4), n = 152
IFI16 (rs1057028)	Genotypic	A/A	125 (57.3)	76 (50.7)	1.00	0.14	463.7
		A/T	58 (26.6)	40 (26.7)	1.20 (0.71-2.03)
		T/T	35 (16.1)	34 (22.7)	1.81 (1.01-3.23)
	Allelic	A	316 (71)	196 (64)	1.00	0.91	NA
		T	130 (29)	108 (36)	1.24 (0.91-0.68)
	Dominant	A/A	125 (57.3)	76 (50.7)	1.00	0.12	463.2
		A/T-T/T	93 (42.7)	74 (49.3)	1.43 (0.91-2.22)
	Recessive	A/A-A/T	183 (83.9)	116 (77.3)	1.00	0.06	462.1
		T/T	35 (16.1)	34 (22.7)	1.70 (0.98-2.96)

SNP: Single nucleotide polymorphism; CHC: Chronic hepatitis C; AIC: Akaike Information Criterion; NA: Not available.

Table 3 Allele/genotypic distribution of AIM2 (rs2814770) among chronic hepatitis C patients

SNP	Model	Genotype	CHC patients		OR (95%CI)	P value1	AIC
			Fibrosis grade (F0-F1), n = 70	Fibrosis grade, (F2-F4), n = 70
AIM2 rs2841770	Genotypic	C/C	24 (34.8)	17 (24.3)	1.00	0.05	125.3
		C/T	26 (37.7)	33 (47.1)	2.00 (0.66-6.09)
		T/T	19 (27.5)	20 (28.6)	4.86 (1.27-18.58)
	Allelic	C	75 (54)	67 (48)	1.00	0.40	NA
		T	65 (46)	73 (52)	1.12 (0.79-2.01)
	Dominant	C/C	24 (34.8)	17 (24.3)	1.00	0.058	125.5
		C/T-T/T	45 (65.2)	53 (75.7)	2.66 (0.94-7.50)
	Recessive	C/C-C/T	50 (72.5)	50 (71.4)	1.00	0.038	124.8
		T/T	19 (27.5)	20 (28.6)	3.13 (1.03-9.56)

¹Genotypic distribution and Recessive model were significantly associated with increased hepatic fibrosis risk.

SNP: Single nucleotide polymorphism; CHC: Chronic hepatitis C; AIC: Akaike Information Criterion; NA: Not available.

Table 4 Combined genotype analysis of IFI16 (rs1057028) and AIM2 (rs2814770) variant associated with risk of liver fibrosis

Combined genotypes rs1057028 A/T, rs2814770 C/T	Frequency	Case, control ratios	OR (95%CI interval)	P value corrected1
A-C	0.3673	0.2595, 0.4703	1.00	-
A-T	0.2874	0.2905, 0.294	2.60 (1.16-5.86)	0.022
T-T	0.2054	0.231, 0.1703	2.41 (0.98-5.91)	0.057
T-C	0.1399	0.219, 0.0654	2.40 (0.74-7.82)	0.15

¹The combined effect of both A allele of IFI16 rs1057028 and T allele of AIM2 rs2814770 were significant predictors of liver fibrosis risk.

Table 5 Association of IFI16 (rs1057028) with different baseline clinical and laboratory characteristics of hepatitis C virus induced liver fibrosis patients under recessive model

Measure	IFI16 (rs1057028) recessive model		P value
	A/A + A/T (n = 309)	T/T (n = 69)
Age (years)	40 (32-50)	40 (33-45)	0.87
Gender
Female	153 (80.95)	36 (19.05)	0.7
Male	155 (82.45)	33 (17.55)
BMI (kg/m2)	26.85 (24-30)	26.8 (24-30.7)	0.68
HCV-RNA log10 (IU/mL)	4.57 (3.7-5.4)	4.75 (5.4-3.7)	0.86
ALT (IU/L)	60 (39-88)	57 (42-94.5)	0.69
AST (IU/L)	56 (40-83)	51 (38.5-83.5)	0.63
Bilirubin (mg/dL)	0.8 (0.7-0.9)	0.8 (0.7-0.95)	0.22

Data were showed as n (%) or median (interquartile range). BMI: Body mass index; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 6 Association of AIM2 (rs2814770) with different baseline characteristics of hepatitis C virus induced liver fibrosis patients

Measure	AIM2 (rs2814770) recessive model		P value1
	C/C + C/T (n = 101)	T/T (n = 39)
Age (years)	38 (31-48.7)	40 (30-48)	0.54
Gender
Female	54 (77.1)	16 (22.9)	0.18
Male	47 (67.1)	23 (32.9)
BMI (kg/m2)	27.2 (23.8-30.9)	24.5 (22.4-29.4)	0.05
HCV-RNA log10 (IU/mL)	4.7 (3.8-5.3)	4.67 (3.9-5.4)	0.89
ALT (IU/L)	57 (37-89.5)	61 (42-98)	0.21
AST (IU/L)	53 (40.2-80.7)	62.5 (35-86.2)	0.37
Bilirubin (mg/dL)	0.8 (0.7-0.9)	0.8 (0.7-0.95)	0.45

¹Body mass index were significant predictor of liver fibrosis risk.

Data were showed as n (%) or median (interquartile range). BMI: Body mass index; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 7 Univariate Logistic regression analysis of independent factors associated with liver cirrhosis

Factors	OR (95%CI)1	P value2
Age	1.060 (1.03-1.08)	0.000
Gender	0.916 (0.53-1.8)	0.916
BMI	1.07 (1.01-1.13)	0.017
HCV-RNA log10	0.96 (0.75-1.24)	0.741
ALT	1.007 (1.00-1.01)	0.017
AST	1.000 (0.99-1.00)	0.891
Total bilirubin	1.196 (0.82-1.74)	0.352
IFI16 rs1057028 (TT)	1.22 (0.56-2.67)	0.607

¹The overall model explains that predictors have 67% variance in disease risk.

²Age, body mass index and alanine aminotransferase levels were statistically significant independent predictors of liver cirrhosis.

Nagelkerke R² = 0.67, -2 Log likelihood = 320.935 and P = 0.07. BMI: Body mass index; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.