Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis
- Author:
- No author available
- Journal Title:
- World Journal of Gastroenterology
- Issue:
- 22
- DOI:
- 10.3748/wjg.v18.i22.2813
- Key Word:
- Fatty liver;Fibrosis;Hemochromatosis;HFE protein;Iron overload;Patatin-like phospholipase domain containing-3 gene;Steatosis
Abstract： AIM:To investigate whether the patatin-/ike phospho/ipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis,fibrosis stage,and cirrhosis in hereditary hemochromatosis (HH).METHODS:We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy,for whom the presence of cirrhosis could be determined based on histological or clinical criteria,without excessive alcohol intake (＜ 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis.Steatosis was evaluated in 123 patients by histology (n =100) or ultrasound (n =23).The PNPLA3 rs738409 single nucleotide polymorphism,encoding for the p.148M protein variant,was genotyped by a Taqman assay (assay on demand,Applied Biosystems).The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis,fibrosis stage,and cirrhosis was evaluated by logistic regression analysis.RESULTS:PNPLA3 genotype was not associated with metabolic parameters,including body mass index (BMI),the presence of diabetes,and lipid levels,but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele,95％ confidence interval (CI):1.05-3.31;P =0.037],independently of BMI and alanine aminotransaminase (ALT) levels.The p.148M variant was also associated with higher aspartate aminotransferase (P =0.0014) and ALT levels (P =0.017) at diagnosis,independently of BMI and the severity of iron overload.In patients with liver biopsy,the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27,P =0.041).In the overall series of patients,the p.148M variant was associated with cirrhosis in lean (P =0.049),but not in overweight patients (P =not significant).At logistic regression analysis,cirrhosis was associated with BMI ≥ 25 (OR 1.82,95％ CI:1.02-3.55),ferritin ＞ 1000 ng/mL at diagnosis (OR 19.3,95％ CI:5.3-125),and with the G allele in patients with BMI ＜ 25 (OR 3.26,95％ CI:1.3-10.3).CONCLUSION:The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH.
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