March 20, 2015Scientific Reports146 citationsOpen Access

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

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Nonalcoholic fatty liver disease (NAFLD) (n=16437). Intervention: PNPLA3 rs738409 polymorphism vs. Controls without the polymorphism. Primary outcome: Nonalcoholic fatty liver disease (NAFLD) risk (additive model) (OR 3.41, 95% CI 2.57-4.52, p=<0.00001).

RXRenfan Xu ATAnyu Tao SZShasha Zhang

Key Result

The PNPLA3 rs738409 polymorphism was significantly associated with an increased risk of nonalcoholic fatty liver disease (OR 3.41) and nonalcoholic steatohepatitis (OR 4.44).

Study Design

Type

Meta-Analysis (n=16,437)

PICO

Population

16,437 individuals (6,071 NAFLD patients and 10,366 controls) from 23 case-control studies evaluating the association between the PNPLA3 rs738409 polymorphism and NAFLD.

Exposure / Comparator

PNPLA3 rs738409 polymorphism vs Controls without the polymorphism

Primary Outcome

Nonalcoholic fatty liver disease (NAFLD) risk (additive model) — OR 3.41 (2.57-4.52), p=<0.00001

Main Result

Odds Ratio: 3.41 (95% CI 2.57–4.52)

p-value: p=<0.00001

Limitations

Retrieved literature may not be sufficiently comprehensive as only published case-control studies were included.
Most study subjects were of Caucasian and Asian ancestry, with a very limited Hispanic subgroup.
Potential selective bias and publication bias.
Potential effects of gene-gene and gene-environment interactions were not fully considered.
The sample size of NASH was small, limiting statistical power for definitive conclusions.

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.

问 AI

Bookmark

View Full Paper

Cite This Study

Xu et al. (Fri,) conducted a meta-analysis in Nonalcoholic fatty liver disease (NAFLD) (n=16,437). PNPLA3 rs738409 polymorphism vs. Controls without the polymorphism was evaluated on Nonalcoholic fatty liver disease (NAFLD) risk (additive model) (OR 3.41, 95% CI 2.57-4.52, p=<0.00001). The PNPLA3 rs738409 polymorphism was significantly associated with an increased risk of nonalcoholic fatty liver disease (OR 3.41) and nonalcoholic steatohepatitis (OR 4.44).

synapsesocial.com/papers/6a74b81cb35e02fb15032e41 https://doi.org/https://doi.org/10.1038/srep09284

问 AI

Bookmark

View Full Paper