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

J Physiol Anthropol. 2019 Sep 5;38(1):12. doi: 10.1186/s40101-019-0204-3.

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 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).

Conclusions: This cross-sectional study suggests that Mt5178 C/A polymorphism modulates the effects of physiological aging on kidney function in Japanese men.

Keywords: Estimated glomerular filtration rate; Kidney function; Longevity; Mitochondrial DNA polymorphism; NADH dehydrogenase; Physiological aging.

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Asian Continental Ancestry Group / statistics & numerical data
  • Cross-Sectional Studies
  • DNA, Mitochondrial / genetics*
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Japan / epidemiology
  • Longevity / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*

Substances

  • DNA, Mitochondrial