Longevity-associated mitochondrial DNA 5178 C/A polymorphism and its interaction with cigarette consumption are associated with pulmonary function in middle-aged Japanese men

Abstract

Pulmonary function is a crucial factor associated with longevity. Mitochondrial DNA 5178 cytosine/ adenine (Mt5178 C/A) polymorphism is reported to be associated with longevity in the Japanese population. We have previously reported that Mt5178 C/A polymorphism is widely associated with physiological and biochemical status. The objective of this study was to investigate whether Mt5178 C/A polymorphism is associated with pulmonary function. The subjects were 463 Japanese men (mean age ± SD 54.0 ± 7.6 years). Genotyping of Mt5178 C/A was performed by polymerase chain reaction-restriction fragment length polymorphism. A cross-sectional study of the relationship between genotype and spirometric data, namely forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ), was conducted. Among younger subjects (age <55 years), FVC and FEV 1 were significantly higher for men with Mt5178A than for those with Mt5178C. Interaction between Mt5178 C/A polymorphism and smoking habits in FEV 1 /FVC ratio was observed. Cigarette consumption (pack-years of smoking) was significantly and negatively associated with FEV 1 / FVC ratio for men with Mt5178C. Among older subjects (age ‡55 years), FEV 1 /FVC ratio was significantly lower for current smokers with Mt5178C than for never smokers with Mt5178C or for never smokers with Mt5178A. Mt5178 C/A polymorphism and its interaction with cigarette consumption may be associated with pulmonary function in Japanese men.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study

“…Except for respiratory function [14], the effects of cigarette smoking on clinical or subclinical findings are more apparent in men with ND2-237Met than in those with ND2-237Leu [15-18]. Cigarette smoking increases the risk of hyper-low-density lipoprotein (LDL) cholesterolemia or that of hypertriglyceridemia in men with ND2-237Met [15].…”

“…Considering our results together with hyper-LDL cholesterolemia, hypertriglyceridemia and high levels of non-HDL cholesterol as risk factors for atherosclerotic diseases [27], habitual smoking may offset the antiatherogenic properties of ND2-237Met genotype. Among ND2-237Leu genotypic men, although cigarette consumption appears to reduce the risk of raised levels of serum ALT, it increases the risk of chronic obstructive pulmonary disease [14]. Therefore, smoking cessation is also recommended for them.…”

“…Second, we analyzed only a single population, and to avoid errors in molecular epidemiological survey, it is necessary to analyze two or more independent data sets. Third, although similar subject selections have been applied in our previous studies [9,14-19,37], selection bias cannot be ruled out. Fourth, as this was a cross-sectional study, and it can indicate causal links, it cannot establish valid causality.…”

“…Japanese individuals with ND2-237Met are more resistant to lifestyle-related adult-onset diseases, such as hypertension [9], diabetes [10], myocardial infarction [11,12] and cerebrovascular disorders [13], than those with ND2-237Leu. Moreover, ND2-237 Leu/Met polymorphism modulates the effects of cigarette smoking on respiratory function [14], the risk of dyslipidemia [15], serum non-high-density lipoprotein (non-HDL) cholesterol levels [16], hematological parameters [17] and intraocular pressure [18]. However, there has been no research on the interactive effects of ND2-237 Leu/Met polymorphism and cigarette smoking on serum liver enzyme levels; specifically, serum aspartate aminotransferase (AST) levels, serum alanine aminotransferase (ALT) levels or serum gamma-glutamyltransferase (GGT) levels.…”

Association of the mt-ND2 5178A/C polymorphism with Parkinson’s disease

“…However, to date, no consistent association has been demonstrated between mutations in the mtDNA and PD [14]. Previously, a cytosine to adenine transversion at position 5178 in the mtDNA, which results in a leucine to methionine amino acid substitution in the second subunit of complex I (mt-ND2 ) has been associated with increased longevity [15] as well as resistance against a number of other conditions such as hypertension [16], atherosclerosis [17], dyslipidemia [18], type 1 diabetes [19], and pulmonary function [20]. Recently the D4a haplogroup has also been suggested to reduce the risk of ischemic stroke in a Chinese population [21].…”