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

Kentaro Oniki,Yasuhiro Ogata,Tomoko Izuka,Koji Otake,Kazuko Nakagawa,Junji Saruwatari,Misaki Sakata,Ayami Kajiwara,Kazunori Morita,Silvia C. Sookoian

doi:10.1371/journal.pone.0132640

Kentaro Oniki, Yasuhiro Ogata + Show 8 more

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https://doi.org/10.1371/journal.pone.0132640

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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.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is a major health problem because the prevalence is increasing worldwide and the presence is an early predictor of future type 2 diabetes, PLOS ONE | DOI:10.1371/journal.pone.0132640 July 22, 2015Association among patatin-like phospholipase 3 (PNPLA3), NAFLD and estimated glomerular filtration rate (eGFR) in Normal Weight
Among the subjects included in the cross-sectional analyses, the mean values of the body mass index (BMI), waist circumstance, fasting blood glucose, diastolic blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), TG, AST, ALT, gamma-glutamyl transferase (GGT), the prevalence of being overweight, diabetes, dyslipidemia, ever-smoking status and the frequencies of PNPLA3 C/G or G/G genotypes were significantly higher in the NAFLD subjects than in the non-NAFLD subjects, whereas the age, high-density lipoprotein cholesterol (HDL-C) and the frequency of females were significantly lower (Table 1)
Among the subjects included in the longitudinal analyses, the mean values of the BMI, waist circumstance, fasting blood glucose, TG, AST, ALT, GGT, the prevalence of being overweight, diabetes and dyslipidemia were significantly higher in the NAFLD subjects than in the non-NAFLD subjects at baseline, whereas the value of HDL-C was significantly lower (Table 1)

Summary

Objectives

We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while paying careful attention to the weight status of the subjects

Methods

Results

Conclusion