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

• Published in: PloS one Vol. 10; no. 7; p. e0132640
• Main Authors: Oniki, Kentaro, Saruwatari, Junji, Izuka, Tomoko, Kajiwara, Ayami, Morita, Kazunori, Sakata, Misaki, Otake, Koji, Ogata, Yasuhiro, Nakagawa, Kazuko
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.07.2015; Public Library of Science (PLoS)
• Subjects: Aged; Alcohol use; Alcoholic beverages; Analysis; Asian people; Asian People - genetics; Body mass; Body mass index; Body size; Body weight; Cardiovascular disease; Carriers; Correlation analysis; Cross-Sectional Studies; Diabetes; Epidermal growth factor receptors; Fatty liver; Female; Gene polymorphism; Genetic aspects; Genetic Predisposition to Disease; Genotypes; Glomerular Filtration Rate; Hepatitis; Hepatitis B; Humans; Indexing; Japan; Kidney diseases; Kidney Function Tests; Lipase - genetics; Liver; Liver diseases; Longitudinal Studies; Male; Medical screening; Membrane Proteins - genetics; Metabolic disorders; Metabolism; Middle Aged; Non-alcoholic Fatty Liver Disease - genetics; Obesity; Overweight; Overweight - genetics; Pharmaceutical sciences; Pharmacology; Phospholipase; Polymorphism; Polymorphism, Single Nucleotide; Regression analysis; Regression coefficients; Renal function; Retrospective Studies; Risk; Viruses; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0132640

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.