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

<div><p>We investigated the possible association between genetic variants in the Patatin like phospholipase-3 (<em>PNPLA3</em>) gene and nonalcoholic fatty liver disease (NAFLD) in a Han Chinese population. We evaluated twelve tagging single-nucleotide polymorphisms (tSNPs) of the <em>PNPLA3</em> 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 CAAGAA<b>TG</b>CGTG and CGAAGG<b>TG</b>TCCG haplotypes conferred a statistically significant increased risk for NAFLD, while the CGGGAA<b>CC</b>CGCG 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 <em>PNPLA3</em> genetic polymorphisms might influence the susceptibility to NAFLD development independently or jointly in Han Chinese.</p> </div

Associations between risk of NAFLD and frequencies of inferred haplotypes on the basis of the observed genotypes in NAFLD cases and controls.

a<p>In the order of rs738407, rs734561, and rs2006943);</p>b<p>In the order of rs1883350, rs2076208, rs3810622 and rs2294918;</p>c<p>In the order of rs2076212, rs139047, rs9625961, rs738407, rs734561, rs2006943, rs139051, rs738409, rs1883350, rs2076208, rs3810622, and rs2294918.</p>d<p>p value was adjusted by multiple comparisons corrections; e:OR (odds ratio) was adjusted for sex, age, body mass index and other clinical characteristics; CI: confidence interval.</p>f<p>All other haplotypes that had frequency <2% in either cases or controls were pooled.</p

Association between the genotypes of rs738409 and rs139051 and risk of NAFLD.

<p>n: number of individuals; OR (odds ratio) was determined using logistic regression and adjusted for sex, age, body mass index and other clinical characteristics; CI: confidence interval.</p>a<p>P-value based on the Wald test.</p

Cumulative effect of adverse genotypes in PNPLA3 rs738409 and rs139051 on NAFLD.

a<p>Risk genotypes were GC/GG for rs734089 and TT for rs139051.</p>b<p>Individuals with no risk genotype were set as the reference group. OR (odds ratio) was determined using logistic regression and adjusted for sex, age, body mass index and other clinical characteristics; CI: confidence interval.</p>c<p><i>P</i>-value based on the Wald test;</p

Combined effects^a of <i>PNPLA3</i> polymorphisms and environmental and ‘internal’ exposures on the risk of NAFLD.

a<p>Included ORs and their corresponding 95% CIs.</p>b<p>Adjusted for age, sex, education, marriage, smoking, income status, and other confounding characteristics.</p