Polymorphism In PNPLA3 Rs738409 Is Associated With Hereditariness To Nonalcoholic Fatty Liver Disease

Objective:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. The etiology is believed to be multifactorial with genetic, environmental and psychosocial components, in particular genetic factors. Recently, multiple studies have revealed the gene polymorphism of the PNPLA3 rs738409 (I148M) is closely linked to the genetic susceptibility and progress of liver damage. But there was lack of large samples in china, so we analyzed the Han population’s polymorphism features in PNPLA3 gene of Qingdao, Shandong Province, to explore the relationship betweetn PNPLA3 gene and hereditariness to nonalcoholic fatty liver disease.Methods:The study included 315 cases of patients with NAFLD and 336 cases of healthy control subjects. We detected sequence fragments of PNPLA3 gene polymorphism both in NAFLD group and control group, by collecting their pathography and biochemical results, extracting DNA from whole blood, utilizing the polymerase chain reaction (PCR) and gene sequencing orderly, and according to their sequence fragments, we can determine their genotype. Whether each genotype of the NAFLD group and control group has group representation or not was based on Hardy-weinbeurg genetic equilibrium analysis, and the relationship between genetic mutations and NAFLD-related factors were analyzed by non-conditional Logistic regression. In addition, SPSS 11.5 software was used for statistical analysis.Results:There exists PNPLA3 gene polymorphism-rs738409(I148M) in Chinese population. Allele frequency distribution of rs738409 G were 65.40%,71.87% and 56.47% in patients with NAFLD, NASH and SS and 33.18% in control, respectively, which had statistical signification(P<0.05). Non-conditional Logistic regression showed, comparing with 148CC gene carriers, odds ratio of occurrence of NAFLD was 3.81(95% CI:3.03 to 4.79, P<0.05), and the odds ratio of occurrence of NASH OR was 1.97 (95% CI= 1.41-2.75, P<0.05) in 148GG gene carriers. Rs738409 polymorphism of the PNPLA3 gene is associated with the level of serum ALT、γ-GT. Through stratified analysis of NASH group, the BMI, ALT, and FINS of 148GG genotype are all higher than that of the 148CC genotype (P<0.05), while the serum HDL level of 148GG genotype is lower than that of both 148CC genotype and 148GC genotype (P<0.05), all of which suggests that allele G is linked with liver inflammation and the increase of liver fat.Conclusion:The results suggested that I148M, a PNPLA3 gene polymorphism, is associated with NAFLD hereditary susceptibility, which is a significant factor in determining NAFLD hereditary susceptibility, in Chinese population.