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Meta-Analysis
. 2019 Feb;98(7):e14324.
doi: 10.1097/MD.0000000000014324.

Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) susceptibility and severity: A meta-analysis

Guangrong Dai  1   2 , Pengfei Liu  1 , Xiaomei Li  1 , Xiaoyan Zhou  2 , Shuixiang He  2
Affiliations
Meta-Analysis

Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) susceptibility and severity: A meta-analysis

Guangrong Dai et al. Medicine (Baltimore). 2019 Feb.

Abstract

Objective: This meta-analysis is to investigate the relationship between the patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism and the susceptibility and severity of nonalcoholic fatty liver disease (NAFLD).

Methods: Chinese Journal Full-text Database, Wanfang Database, VIP Database, and PubMed Database were subjected to case-control study retrieving, from January 2008 to December 2014. Following key words were used: fatty liver, PNPLA3, and rs738409 gene or variants or polymorphism or alleles. Meta-analysis was performed based on the retrieved articles.

Results: In total 65 studies were first retrieved according to the key words, and finally 21 studies with 14,266 subjects were included. Meta-analysis showed that PNPLA3 rs738409 polymorphism exerted strong influence not only on fatty liver but also on the histological injury. PNPLA3 rs738409 [G] allele was a risk factor for NAFLD (GG vs CC, OR = 4.01, 95% CI 2.93-5.49; GC vs CC, OR = 1.88, 95% CI 1.58-2.24). PNPLA3 gene variant was significantly associated with the increased serum alanine aminotransferase (ALT) levels (GG vs CC, standardized mean difference = 0.47, 95% CI 0.14-0.81). In addition, nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers (GG vs CC, OR = 3.24, 95% CI 2.79-3.76; GC vs CC, OR = 2.14, 95% CI 1.43-3.19).

Conclusion: PNPLA3 rs738409 polymorphism is not only a factor significantly associated with the susceptibility of NAFLD, but also related to the susceptibility of aggressive diseases.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Article retrieving and screening process.
Figure 2
Figure 2
Forest plots for association between PNPLA3 rs738409 polymorphism and NAFLD susceptibility (20 articles). A, GG versus CC. B, GC versus CC. Wagebknecht b represented African-American population, and Valenti b represented adults.
Figure 3
Figure 3
Forest plots for association between PNPLA3 rs738409 polymorphism and NAFLD susceptibility (16 articles after exclusion). A, GG versus CC. B, GC versus CC. Wagebknecht b represented African-American population, and Valenti b represented adults.
Figure 4
Figure 4
Forest plots for association between PNPLA3 rs738409 polymorphism and NAFLD susceptibility based on age sub-group analysis (16 articles). A, GG versus CC. B, GC versus CC.
Figure 5
Figure 5
Forest plots for association between PNPLA3 rs738409 polymorphism and NAFLD susceptibility based on race subgroup analysis (16 articles). A, GG versus CC. B, GC versus CC.
Figure 6
Figure 6
Forest plots for association between PNPLA3 rs738409 polymorphism and ALT level in NAFLD patients (7 articles). A, GG versus CC. B, GC versus CC.
Figure 7
Figure 7
Forest plots for association between PNPLA3 rs738409 polymorphism and NASH (6 articles). A, GG versus CC. B, GC versus CC.
Figure 8
Figure 8
Funnel plots for association between PNPLA3 rs738409 polymorphism and NAFLD susceptibility (20 articles). A, GG versus CC. B, GC versus CC.
Figure 9
Figure 9
Funnel plots for association between PNPLA3 rs738409 polymorphism and ALT level in NAFLD patients (7 articles). A, GG versus CC. B, GC versus CC.
Figure 10
Figure 10
Funnel plots for association between PNPLA3 rs738409 polymorphism and NASH (6 articles). A, GG versus CC. B, GC versus CC.
See this image and copyright information in PMC

References

    1. Aragones G, Auguet T, Armengol S, et al. PNPLA3 expression is related to liver steatosis in morbidly obese women with non-alcoholic fatty liver disease. Int J Mol Sci 2016;17: E630. - PMC - PubMed
    1. Tai CM, Huang CK, Tu HP, et al. Interactions of a PPARGC1A variant and a PNPLA3 variant affect nonalcoholic steatohepatitis in severely obese Taiwanese patients. Medicine (Baltimore) 2016;95:e3120. - PMC - PubMed
    1. Fan JH, Xiang MQ, Li QL, et al. PNPLA3 rs738409 polymorphism associated with hepatic steatosis and advanced fibrosis in patients with chronic hepatitis c virus: a meta-analysis. Gut Liver 2016;10:456–63. - PMC - PubMed
    1. Sookoian S, Castano GO, Burgueno AL, et al. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J Lipid Res 2009;50:2111–6. - PMC - PubMed
    1. Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 2010;52:904–12. - PMC - PubMed

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