Genetic Variants in PNPLA3 and Risk of Non-Alcoholic Fatty Liver Disease in a Han Chinese Population

Abstract

We investigated the possible association between genetic variants in the Patatin like phospholipase-3 (PNPLA3) gene and nonalcoholic fatty liver disease (NAFLD) in a Han Chinese population. We evaluated twelve tagging single-nucleotide polymorphisms (tSNPs) of the PNPLA3 gene in a frequency matched case–control study from Fuzhou city of China (553 cases, 553 controls). In the multivariate logistic regression analysis, the rs738409 GG or GC, and rs139051 TT genotypes were found to be associated with increased risk of NAFLD, and a significant trend of increased risk with increasing numbers of risk genotype was observed in the cumulative effect analysis of these single nucleotide polymorphisms. Furthermore, haplotype association analysis showed that, compared with the most common haplotype, the CAAGAATGCGTG and CGAAGGTGTCCG haplotypes conferred a statistically significant increased risk for NAFLD, while the CGGGAACCCGCG haplotype decreased the risk of NAFLD. Moreover, rs738409 C>G appeared to have a multiplicative joint effect with tea drinking (P<0.005) and an additive joint effect with obesity (Interaction contrast ratio (ICR) = 2.31, 95% CI: 0.7–8.86), hypertriglyceridemia (ICR = 3.07, 95% CI: 0.98–5.09) or hypertension (ICR = 1.74, 95% CI: 0.52–3.12). Our data suggests that PNPLA3 genetic polymorphisms might influence the susceptibility to NAFLD development independently or jointly in Han Chinese.

The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis

“…Other reports have examined the association between the PNPLA3 rs738409 C>G polymorphism and other forms of liver disease, most notably NAFLD, which leads to United States, Taiwan, China, Japan, or Malaysia (39)(40)(41)(42)(43). Indeed, in a Japanese study, Hotta et al ( 44 ) found that the risk of carrying the G allele was 0.44 in control patients and 0.60 in patients with NAFLD.…”

Composite prognostic models across the non-alcoholic fatty liver disease spectrum: Clinical application in developing countries

“…Two seminal population-based genome-wide association studies (GWAS) conducted in 2008 [137,138] identified a common non-synonymous single-nucleotide polymorphism in the patatin-like phospholipase domaincontaining protein 3 (PNPLA3) gene (rs738409 C > G; I148M), which encodes the multifunctional lipolytic enzyme adiponutrin (ADPN) [139] as a major determinant of inter-individual variation in hepatic fat content and plasma liver enzyme levels. The PNPLA3 rs738409 SNP has subsequently been reproducibly associated with increased susceptibility towards the onset and progression of NAFLD across boundaries for age, sex and ethnic background [139][140][141][142][143][144] . Findings from at least two recent meta-analyses have also confirmed the clinical relevance of PNPLA3 rs738409 as a potent genetic risk factor for NASH, severe hepatic fibrosis and hepatocellular carcinoma [145,146] .…”

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

“…Polymorphisms of PNPLA3 gene have been found to be strongly associated with the pathogenic status of NAFLD in different populations [91][92][93] . PNPLA3 gene, encoding adiponutrin is known to have lipase activity in vitro and has been found to be involved in glucose and lipid metabolism [91] .…”