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

Abstract

Background Mitochondrial 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. Methods A 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). Results In 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 m 2 , 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 m 2 , reduced eGFR was dependent on aging only in Mt5178C genotypic men ( P for trend < 0.001). Conclusions This cross-sectional study suggests that Mt5178 C/A polymorphism modulates the effects of physiological aging on kidney function in Japanese men.

Association of m.5178C&gt;A variant with serum lipid levels: a systematic review and meta-analysis

“…Notably, this hypothesis was verified by an emerging study conducted by Tian et al [12], in which, variant of m.5178C>A decreased ROS production and Caspase 3/7 activity, increased ATP production and membrane potential, and resistance to apoptosis. All these protective effects caused by this polymorphism demonstrated that variant of m.5178C>A was related to increased mitochondrial functions, which might benefit lipid metabolism [13][14][15][41][42][43][44].…”

“…Moreover, an emerging study [12] reported that m.5178C>A variant was associated with improved mitochondrial functions. Intriguingly, the improvement of mitochondrial functions was associated with ameliorated lipid metabolism [13][14][15]. When combined with the above speculation, a variant of m.5178C>A may benefit lipid profile by enhancing mitochondrial functions.…”