Longevity-associated mitochondrial DNA 5178 C/A polymorphism modifies effect of aging on renal function in male Japanese health checkup examinees: an exploratory cross-sectional study

Iichiro Ohtsu,Hirotaka Ochiai,Takako Shirasawa,Naomi Matsunaga,Shogo Sai,Mamoru Ishikawa,Akira Minoura,Takahiko Yoshimoto,Masao Yoshida,Akatsuki Kokaze,Kanae Karita

doi:10.1186/s40101-019-0204-3

Abstract

BackgroundMitochondrial DNA 5178 (Mt5178) C/A polymorphism is reportedly associated with longevity in the Japanese population. The objective of this study was to investigate whether Mt5178 C/A polymorphism influences the effect of physiological aging on renal function in male Japanese health checkup examinees.MethodsA total of 404 male subjects (mean age ± SD, 53.9 ± 7.8 years; range, 29–76 years) were selected from among individuals visiting the hospital for regular medical checkups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and aging on renal function was then conducted. Renal function was evaluated by estimated glomerular filtration rate (eGFR). Subjects were divided into three age groups (< 50, 50–59, ≥ 60 years).ResultsIn simple linear regression analysis, a significant negative association between aging and eGFR was observed in both Mt5178C and Mt5178A genotypic men (P < 0.001 and P = 0.003, respectively). However, in multiple linear regression analysis, a significant effect of aging on reduced eGFR was observed only in Mt5178C genotypic men (P < 0.001). Logistic regression analysis showed that, in the case of reduced eGFR defined as < 75 mL/min/1.73 m2, reduced eGFR was dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.002, respectively). After adjusting for smoking status and alcohol consumption, reduced eGFR was also dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.014, respectively). However, in reduced eGFR defined as < 90 mL/min/1.73 m2, reduced eGFR was dependent on aging only in Mt5178C genotypic men (P for trend < 0.001).ConclusionsThis cross-sectional study suggests that Mt5178 C/A polymorphism modulates the effects of physiological aging on kidney function in Japanese men.

Highlights

Mitochondrial DNA 5178 (Mt5178) C/A polymorphism is reportedly associated with longevity in the Japanese population
Our previous research reported that Mt5178 C/A polymorphism modulates the effect of alcohol consumption [15] or green tea consumption [16] on renal function, evaluated by estimated glomerular filtration rate (GFR)
60 years than in those aged < 50 years. In this exploratory cross-sectional study, we found that longevity-associated Mt5178 C/A polymorphism modifies the effect of aging on renal function

Summary

Introduction

Mitochondrial DNA 5178 (Mt5178) C/A polymorphism is reportedly associated with longevity in the Japanese population. Physiological aging, even in healthy aging, is associated with changes in kidney function, for example, glomerular filtration rate (GFR), sodium resorption, transtubular potassium gradient, urinary concentration, renal vascular resistance, and plasma flow [1,2,3]. Among these physiological changes, a decline in GFR with normal aging is widely known [1, 2]. An association between Mt5178 C/A polymorphism and physiological aging effect on pulmonary function was reported [17], an association between Mt5178 C/A polymorphism and effect of physiological aging on kidney function has not yet been reported

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