ABSTRACT
OBJECTIVE: The mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may exert anti-atherogenic effects. The aim of this study was to determine whether there were longitudinal differences in serum lipid levels between carriers of the Mt5178C genotype and those of the Mt5178A genotype and to assess the impact of these genotypes on serum cholesterol levels. METHODS: The serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were measured and the Mt5178 C/A genotypes determined in 110 Japanese men aged 41-66 (mean 52.3) years who had received medical checkups twice in the period 1999-2005. The longitudinal changes of TC, HDLC, and LDLC were calculated according to genotype. RESULTS: The serum levels of TC at baseline and follow-up were significantly different, whereas those of HDLC and LDLC were not. The changes in HDLC differed significantly between the two Mt5178 C/A genotype groups, with the changes in HDLC level being significantly greater in the Mt5178A genotype group than in the Mt5178C group (p = 0.015). CONCLUSIONS: The Mt5178 C/A genotype may modify longitudinal changes in serum TC and HDLC levels in middle-aged Japanese men.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , DNA, Mitochondrial/genetics , NADH Dehydrogenase/genetics , Polymorphism, Genetic , Adenine/chemistry , Cytosine/chemistry , Humans , Japan , Longitudinal Studies , Male , Middle Aged , Polymerase Chain Reaction , Time FactorsABSTRACT
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 >or=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.
Subject(s)
Asian People/genetics , DNA, Mitochondrial/genetics , Forced Expiratory Volume/genetics , Longevity/genetics , Smoking , Vital Capacity/genetics , Adenine/chemistry , Cytosine/chemistry , Humans , Lung/physiology , Male , Middle Aged , Polymorphism, GeneticABSTRACT
NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in the Japanese population, and the ND2-237Met genotype may exert antiatherogenic effects. To investigate whether ND2-237 Leu/Met polymorphism is associated with risk of hypertension, we conducted a cross-sectional study of 398 Japanese male subjects. The frequency of hypertension was significantly higher in ND2-237Leu genotypic men than in ND2-237Met genotypic men. On analysis of covariance, the interaction between ND2-237 Leu/Met polymorphism and habitual drinking was significantly associated with both systolic blood pressure and diastolic blood pressure. Multiple logistic regression analysis revealed that the ND2-237Met genotype, particularly in younger subjects (age <60 years), had a lower odds ratio for hypertension than the ND2-237Leu genotype. Moreover, the association of ND2-237 Leu/Met polymorphism with hypertension may depend on the frequency of alcohol consumption. The odds ratio for hypertension was significantly higher in daily drinkers with ND2-237Leu when compared with non- or ex-drinkers with ND2-237Leu. However, the association between the ND2-237Met genotype and hypertension may not depend on the frequency of alcohol consumption. The present results suggest that ND2-237 Leu/Met polymorphism is associated with hypertension and that modification of hypertension risk is dependent on alcohol consumption in middle-aged Japanese men.
Subject(s)
Alcohol Drinking/genetics , Hypertension/genetics , Leucine/genetics , Methionine/genetics , NADH Dehydrogenase/genetics , Polymorphism, Restriction Fragment Length , Alcohol Drinking/physiopathology , Asian People/genetics , Blood Pressure/physiology , Cross-Sectional Studies , Genetic Predisposition to Disease , Genotype , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Japan/epidemiology , Male , Middle Aged , NADH Dehydrogenase/metabolism , Protein Subunits , Risk FactorsABSTRACT
NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is reportedly associated with longevity in the Japanese population. The ND2-237Met genotype may confer resistance to cardiovascular and cerebrovascular atherogenic diseases. Hyperuricemia is one of the risk factors for cardiovascular disease. To investigate whether ND2-237 Leu/Met polymorphism is associated with serum uric acid (SUA) levels, we conducted a cross-sectional study in 321 healthy Japanese male subjects. In nonobese (body mass index, BMI<25) male subjects, interaction between ND2-237 Leu/Met genotypes and drinking frequency on SUA levels was observed (P=0.031). The SUA levels were significantly higher in daily drinkers with ND2-237Leu than in non-daily drinkers with ND2-237Leu (P=0.018). In nonobese men, after adjustment for covariates, daily drinkers with ND2-237Leu had a significantly higher odds ratio (OR) for hyperuricemia (SUA> or =6.5 mg/dl: vs. daily drinkers with ND2-237Met, OR=3.26, 95% confidence interval (CI) 1.14-9.29; vs. non-daily drinkers with ND2-237Leu, OR=3.22, 95% CI 1.39-7.45; SUA> or =7.0 mg/dl: vs. non-daily drinkers with ND2-237Met, OR=3.53, 95% CI 1.00-12.4). However, in obese (BMI> or =25) men, no significant interaction between ND2-237 Leu/Met polymorphism and habitual drinking on SUA levels or on the risk for hyperuricemia was observed. These results suggest that ND2-237 Leu/Met polymorphism modulates the effects of daily alcohol consumption on SUA levels in nonobese Japanese men.
