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Association Between Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) Polymorphisms and Nonalcoholic Fatty Liver Disease: A HuGE Review and Meta-Analysis

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Review

Association Between Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) Polymorphisms and Nonalcoholic Fatty Liver Disease: A HuGE Review and Meta-Analysis

Renfan Xu et al. Sci Rep.

Abstract

We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, with assessment for heterogeneity and publication bias. Twenty-three case-control studies involving 6071 NAFLD patients and 10366 controls were identified. The combined results showed a significant association between NAFLD risk and the rs738409 polymorphism in all genetic models (additive model: OR = 3.41, 95% CI = 2.57-4.52; P < 0.00001). In addition, evidence indicated that the rs738409 polymorphism was significantly associated with NASH in all genetic models (additive model: OR = 4.44, 95% CI = 3.39-5.82; P < 0.00001). The subgroup and sensitivity analyses showed that these changes were not influenced by the ethnicities and ages of subjects or by the source of controls. The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models. These findings suggest that the rs738409 polymorphism in PNPLA3 gene confers high cross-ethnicity risk for NAFLD and NASH development.

Figures

Figure 1
Figure 1. Flowchart of the study selection.
Figure 2
Figure 2. Forest plot of NAFLD susceptibility associated with rs738409 polymorphism at additive model (GG vs CC).
Figure 3
Figure 3
(A)The forest plot for the association between rs738409 polymorphism and the risk of necroinflammation (additive model: GG vs CC). (B)The forest plot for the association between rs738409 polymorphism and the risk of fibrosis (additive model: GG vs CC).
Figure 4
Figure 4. Forest plot of simple steatosis susceptibility associated with rs738409 polymorphism at additive model (GG vs CC).
Figure 5
Figure 5. Forest plot of NASH susceptibility associated with rs738409 polymorphism at additive model (GG vs CC).
Figure 6
Figure 6. Publication bias on rs738409 polymorphism under additive model.
(A) Funnel plot of studies of the rs738409 variant and NAFLD. (B) Funnel plot of studies of the rs738409 variant and simple steatosis. (C) Funnel plot of studies of the rs738409 variant and NASH.

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References

    1. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 346, 1221–1231 (2002). - PubMed
    1. Browning J. D. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387–1395 (2004). - PubMed
    1. Farrell G. C. & Larter C. Z. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 43, S99–S112 (2006). - PubMed
    1. Ratziu V., Bellentani S., Cortez-Pinto H., Day C. & Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 53, 372–384 (2010). - PubMed
    1. Powell E. E. et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11, 74–80 (1990). - PubMed
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