Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects - PubMed (original) (raw)

Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

Kentaro Oniki et al. PLoS One. 2015.

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Abstract

In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11-8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1

Fig 1. The longitudinal changes in the prevalence of NAFLD stratified by the PNPLA3 genotype among normal weight subjects.

The prevalence of NAFLD is shown as solid, dashed-dotted and dotted lines in the subjects with the PNPLA3 C/C, C/G and G/G genotypes, respectively. NAFLD, non-alcoholic fatty liver disease; PNPLA3, patatin-like phospholipase 3.

Fig 2

Fig 2. The longitudinal changes in eGFR stratified by the PNPLA3 genotype among normal weight subjects.

The mean values of eGFR are shown as solid, dashed-dotted and dotted lines in the subjects with the PNPLA3 C/C, C/G and G/G genotypes, respectively, and the SEs are shown as antennae. eGFR, estimated glomerular filtration rate; PNPLA3, patatin-like phospholipase 3; SE, standard error.

References

    1. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013; 10: 330–344. 10.1038/nrgastro.2013.41 - DOI - PubMed
    1. Armstrong MJ, Adams LA, Canbay A, Syn WK. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology. 2014; 59: 1174–1197. 10.1002/hep.26717 - DOI - PubMed
    1. Fung J, Lee CK, Chan M, Seto WK, Lai CL, Yuen MF. High prevalence of non-alcoholic fatty liver disease in the Chinese—results from the Hong Kong liver health census. Liver Int. 2015; 35: 542–549. 10.1111/liv.12619 - DOI - PubMed
    1. Ruhl CE, Everhart JE. Fatty liver indices in the multiethnic United States National Health and Nutrition Examination Survey. Aliment Pharmacol Ther. 2015; 41: 65–76. 10.1111/apt.13012 - DOI - PubMed
    1. Liu CJ. Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. J Gastroenterol Hepatol. 2012; 27: 1555–1560. 10.1111/j.1440-1746.2012.07222.x - DOI - PubMed

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