Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis

Table 1 Demographic, anthropometric, clinical, and histological features, as evaluated at diagnosis, of 174 Italian patients with homozygous for the C282Y HFE mutation of hereditary hemochromatosis subdivided according to the PNPLA3 I148M genotype

	All patients	PNPLA3 I148M genotype			Pvalue
		I/I	I/M	M/M
n (%)	174	82 (47)	70 (40)	22 (13)
Age (yr)	47 ± 13	46 ± 13	47 ± 14	50 ± 11	0.22
Gender F (%)	49 (28)	24 (30)	19 (27)	6 (27)	0.79
DAI (g)	10 (0-20)	10 (0-20)	5 (0-20)	10 (0-20)	0.98
BMI (kg/m2)	24 ± 3	24 ± 3	24 ± 3	25 ± 2	0.11
Diabetes (%)	16 (9)	7 (9)	6 (9)	3 (14)	0.57
Total cholesterol (mg/dL)	191 ± 44	197 ± 37	186 ± 50	182 ± 44	0.25
HDL cholesterol (mg/dL)	53 ± 16	53 ± 14	53 ± 17	57 ± 15	0.47
Triglycerides (mg/dL)	120 ± 66	123 ± 64	122 ± 74	99 ± 35	0.30
TS %	80 ± 16	80 ± 16	79 ± 15	81 ± 23	0.94
Ferritin	1000	1018	947	1053	0.36
(ng/mL)	(509-1800)	(490-1813)	(516-1732)	(504-2101)
AST (IU/mL)	34 ± 21	31 ± 16	35 ± 24	44 ± 29	0.019
ALT (IU/mL)	46 ± 32	41 ± 26	47 ± 34	55 ± 45	0.06
GGT (IU/mL)	24 (16-37)	24 (17-37)	24 (15-38)	23 (14-30)	0.95
Steatosis1 (%)	55 (48)	18 (31)	29 (58)	8 (53)	0.014
Advanced fibrosis %	18 (10)	9 (11)	7 (10)	2 (9)	0.95
(Ishak 4) %
Cirrhosis	32 (18)	13 (16)	14 (20)	5 (23)	0.39
(Ishak 5-6) %

¹Available in 123 patients. I: Ileucine; M: Methionine; n: Number; F: Female; DAI: Daily alcohol intake; BMI: Body mass index; HDL: High density lipoprotein cholesterol; TS: Transferrin saturation; AST: Aspartate aminotransferase; ALT: Alanine aminotransaminase; GGT: γ-glutamyl transferase.

Table 2 Independent predictors of steatosis and cirrhosis in Italian patients with homozygous for the C282Y HFE mutation of hereditary hemochromatosis, as evaluated by logistic regression analysis

	OR	95% CI	Pvalue
Independent predictors of steatosis n = 123
BMI (per kg/m2)	1.22	1.06-1.42	0.008
ALT (per IU/mL)	1.01	0.99-1.02	0.353
PNPLA3 genotype (per p allele)	1.84	1.05-3.31	0.037
Independent predictors of cirrhosis n = 174
Ferritin (ng/mL)	1.001	1.000-1.002	< 0.0001
Diabetes	0.54	0.26-1.16	0.101
BMI (>/m2)	1.83	1.02-3.57	0.055
PNPLA3 p allele present (BMI > 25)	0.76	0.37-1.53	0.453
PNPLA3 p allele present (BMI ≤ 25)	3.26	1.28-10.30	0.024

OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; ALT: Alanine aminotransaminase; p.148M: PNPLA3 rs738409 148Met protein variant.

Table 3 Independent predictors of aspartate aminotransferase and alanine aminotransaminase levels in 174 Italian patients with homozygous for the C282Y HFE mutation of hereditary hemochromatosis, in the multivariate generalized linear model

	AST			ALT
	Estimate	95% CI	Pvalue	Estimate	95% CI	Pvalue
Age (yr)	-0.27 ± 0.09	-0.45 - -0.09	0.0034	-0.55 ± 0.14	-0.81 - -0.27	0.0001
TS (%)	0.14 ± 0.07	-0.01 - 0.29	0.063	0.28 ± 0.11	0.05 - 0.50	0.016
Ferritin (ng/mL)	0.01 ± 0.001	0.008 - 0.012	< 0.0001	0.01 ± 0.001	0.009 - 0.014	< 0.0001
GGT (IU/mL)	0.10 ± 0.03	0.03 - 0.16	0.003	0.20 ± 0.05	0.10 - 0.29	< 0.0001
BMI (kg/m2)	0.86 ± 0.42	0.03 - 1.69	0.042	3.36 ± 0.63	2.12 - 4.60	< 0.0001
PNPLA3 genotype (per p.148M allele)	5.46 ± 1.68	2.15 - 8.67	0.0014	6.05 ± 2.51	1.09 - 11.00	0.017

AST: Aspartate aminotransferase; ALT: Alanine aminotransaminase; CI: Confidence interval; TS: Transferrin saturation; GGT: γ-glutamyl transferase; BMI: Body mass index; p.148M: PNPLA3 rs738409 148Met protein variant.

Table 4 Independent predictors of fibrosis stage in 106 Italian patients with homozygous for the C282Y HFE mutation of hereditary hemochromatosis, at ordinal logistic regression analysis

	Estimate	Pvalue
Age (yr)	-0.03 ± 0.02	0.077
Gender (female)	-0.57 ± 0.26	0.029
BMI (kg/m2)	-0.08 ± 0.08	0.311
Diabetes	0.57 ± 0.34	0.09
ALT	-0.02 ± 0.008	0.013
GGT (IU/mL)	0.02 ± 0.01	0.035
Ferritin (ng/mL)	0.0001 ± 0.00	0.421
PNPLA3 genotype (per p.148M allele)	0.56 ± 0.27	0.041

BMI: Body mass index; ALT: Alanine aminotransaminase; GGT: γ-glutamyl transferase; p.148M: PNPLA3 rs738409 148Met protein variant.