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.

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.

NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Influences the Association of Coffee Consumption with Serum Chloride Levels in Male Japanese Health Checkup Examinees: An Exploratory Cross-Sectional Analysis.

BACKGROUND: Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism has been shown to modify the association of coffee consumption with the risk of hypertension, dyslipidemia, and abnormal glucose tolerance, and low serum chloride levels have been shown to be associated with all-cause and cardiovascular disease mortality. Therefore, the purpose of the present study was to investigate whether ND2-237 Leu/Met polymorphism influences the association of coffee consumption with serum chloride levels in male Japanese health checkup examinees. METHODS: From among individuals visiting the hospital for a regular medical checkup, 402 men (mean age ± standard deviation, 53.9 ± 7.8 years) were selected for inclusion in the study. After ND2-237 Leu/Met genotyping, we conducted an exploratory cross-sectional study to examine the combined association of ND2-237 Leu/Met polymorphism and coffee consumption with serum electrolyte levels. RESULTS: After adjusting for age, body mass index, habitual smoking, alcohol consumption, green tea consumption, and antihypertensive medication, coffee consumption significantly increased serum chloride levels (p for trend = 0.001) in men with the ND2-237Leu genotype. After these adjustments, the odds ratios (ORs) for low levels of serum chloride, defined as <100 mEq/L, were found to be dependent on coffee consumption (p for trend = 0.001). In addition, the OR for low levels of serum chloride was significantly lower in men with the ND2-237Leu genotype who consumed ≥4 compared with <1 cup of coffee per day (OR = 0.096, 95% confidence interval = 0.010⁻0.934; p = 0.044). However, neither serum chloride levels nor risk of low levels of serum chloride appeared to be dependent on coffee consumption. CONCLUSIONS: The results suggest that ND2-237 Leu/Met polymorphism modifies the association of coffee consumption with serum chloride levels in middle-aged Japanese men.

Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study.

BACKGROUND: Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. METHODS: A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted. RESULTS: For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as ≥30 U/L; those of serum ALT, as defined as ≥25 U/L; or those of serum GGT, as defined as ≥60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.

Longevity-associated mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters in Japanese men: an exploratory cross-sectional analysis.

BACKGROUND: Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees. METHODS: A total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted. RESULTS: For Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137). CONCLUSIONS: This exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees.

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.

BACKGROUND: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examinees. METHODS: A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After ND2-237 Leu/Met genotyping, a cross-sectional study assessing the combined effects of ND2-237 Leu/Met polymorphism and cigarette smoking on serum aspartate aminotransferase levels, serum alanine aminotransferase (ALT) levels and serum gamma-glutamyltransferase (GGT) levels was then conducted. RESULTS: No statistically significant differences in serum liver enzyme levels among the three smoking status groups (never- or ex-smokers, 1-20 cigarettes smoked per day and >20 cigarettes smoked per day) by ND2-237 Leu/Met genotype were observed. However, for men with ND2-237Met, cigarette smoking significantly increased the risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) (P for trend = 0.031, P for trend = 0.007 and P for trend = 0.004, respectively). After adjustment for age, body mass index, alcohol consumption, coffee consumption, antihypertensive treatment and antidiabetic treatment, a significant association between cigarette smoking and risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) was also observed (P for trend = 0.032, P for trend = 0.019 and P for trend = 0.009, respectively). Surprisingly, for men with ND2-237Leu, cigarette smoking significantly decreased the risk of elevated levels of serum ALT (>30 U/L or ≥25 U/L) (P for trend = 0.026 and P for trend = 0.003, respectively). CONCLUSIONS: Cigarette smoking appears to increase the risk of elevated levels of serum ALT or serum GGT in ND2-237Met genotypic men, but to decrease the risk of elevated levels of serum ALT in ND2-237Leu genotypic men.

Joint effects of mitochondrial DNA 5178 C/A polymorphism and coffee consumption or alcohol consumption on clustering of cardiovascular risk factors in middle-aged Japanese men: a cross-sectional study.

BACKGROUND: Longevity-associated mitochondrial DNA 5178 (Mt5178) C/A reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance, and those of alcohol consumption on the risk of hypertension, dyslipidemia and hyperuricemia in middle-aged Japanese men. However, there has been no research examining whether Mt5178 C/A polymorphism influences the effects of coffee consumption or alcohol consumption on the clustering of cardiovascular risk factors (CRFs). METHODS: A total of 332 male subjects (mean age ± SD, 52.8 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption or alcohol consumption on the clustering of CRFs, namely hypertension, abnormal glucose tolerance, hyper-low-density lipoprotein cholesterolemia, hypo-high density lipoprotein cholesterolemia, hypertriglyceridemia and hyperuricemia, was then conducted. RESULTS: After adjustment for confounding factors, significant and negative associations were observed between coffee consumption and clustering of ≥2 CRFs in subjects with Mt5178C. The adjusted odds ratio (OR) for the clustering of ≥2 or ≥3 CRFs was significantly lower in subjects who consumed 1-3 cups of coffee per day than in those who consumed <1 cup of coffee per day (OR = 0.496, 95% confidence interval (CI): 0.249-0.989, and OR = 0.369, 95% CI: 0.165-0.826, respectively). On the other hand, after adjustment, positive associations between coffee consumption and clustering of ≥2 CRFs were observed in subjects with Mt5178A. However, these associations did not reach a significant level. For Mt5178C genotypic men, the adjusted OR for the clustering of ≥2 or ≥3 CRFs was significantly higher in daily drinkers than in occasional drinkers (OR = 2.737, 95% CI: 1.361-5.502, and OR = 3.024, 95% CI: 1.269-7.210, respectively). On the other hand, the association between Mt5178A genotype and the clustering of ≥2 or ≥3 CRFs did not appear to depend on alcohol consumption. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption or alcohol consumption on the clustering of CRFs in middle-aged Japanese men.

Difference in effects of cigarette smoking or alcohol consumption on serum non-high-density lipoprotein cholesterol levels is related to mitochondrial DNA 5178 C/A polymorphism in middle-aged Japanese men: a cross-sectional study.

BACKGROUND: Mitochondrial DNA 5178 cytosine/adenosine (Mt5178 C/A) polymorphism is associated with longevity in the Japanese. The purpose of this study is to investigate whether Mt5178 C/A polymorphism modifies the effects of habitual smoking or habitual drinking on serum non-high-density lipoprotein (non-HDL) cholesterol levels in middle-aged Japanese men. METHODS: A total of 394 male subjects (age 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and cigarette smoking or alcohol drinking on serum non-HDL cholesterol levels was conducted. High levels of serum non-HDL cholesterol were defined as serum non-HDL cholesterol levels ≥160 mg/dl or ≥190 mg/dl. RESULTS: For men with Mt5178A, cigarette smoking may increase serum non-HDL cholesterol levels (P for trend < 0.001), as well as the risk of high levels of non-HDL cholesterol (serum non-HDL cholesterol levels ≥160 mg/dl, P for trend < 0.001; serum non-HDL cholesterol levels ≥190 mg/dl, P for trend = 0.004). On the other hand, for men with Mt5178C, after adjusting for age and body mass index, alcohol consumption may decrease serum non-HDL cholesterol levels (P for trend = 0.043) and the risk of high levels of non-HDL cholesterol (serum non-HDL cholesterol level ≥160 mg/dl, P for trend = 0.005). CONCLUSIONS: These gene-environment interactions on serum non-HDL cholesterol levels may contribute to the establishment of individualized prevention of the risk of high levels of serum non-HDL cholesterol.

Unexpected combined effects of NADH dehydrogenase subunit-2 237 Leu/Met polymorphism and green tea consumption on renal function in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees. RESULTS: For ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume ≥6 cups of green tea per day than those who consume ≤1 cup of green tea per day (adjusted OR = 5.647, 95% confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR. CONCLUSION: The present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study.

BACKGROUND: Prevention of chronic kidney disease (CKD) is a major public health issue. Although several studies have been performed on the association between alcohol consumption and CKD or renal function, it remains controversial. Numerous genetic polymorphisms have been reported to be associated with CKD and kidney function. Mitochondrial DNA cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in Japanese. This polymorphism modifies the effects of alcohol consumption on blood pressure, risk of hypertension, serum triglyceride levels, risk of hyper-LDL cholesterolemia and serum uric acid levels. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of alcohol consumption on renal function in male Japanese health check-up examinees. METHODS: A total of 394 male subjects aged 29-76 years were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effects of Mt5178 C/A polymorphism and habitual drinking on the risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m(2)) was conducted. RESULTS: For Mt5178A genotypic men, habitual drinking may increase eGFR (P for trend = 0.003) or reduce the risk of mildly decreased eGFR (P for trend = 0.003). Daily drinkers had a significantly higher eGFR than non-drinkers (P = 0.005). The crude odds ratio for decreased eGFR was significantly lower in daily drinkers than in non-drinkers (odds ratio = 0.092, 95% confidence interval: 0.012-0.727, P = 0.024). On the other hand, for Mt5178C genotypic men, habitual drinking does not appear to affect eGFR. CONCLUSION: The present results suggest a joint effect of Mt5178 C/A polymorphism and alcohol consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.

Combined effect of longevity-associated mitochondrial DNA 5178 c/a polymorphism and green tea consumption on risk of hypertension in middle-aged Japanese men.

Mitochondrial DNA 5178 cytosine/adenine (Mt5178C/A) polymorphism is reported to be associated with longevity and to modify the effects of alcohol consumption or coffee consumption on the risk of hypertension in the Japanese population. The objective of this study was to investigate whether Mt5178C/A polymorphism modifies the effects of green tea consumption on blood pressure or risk of hypertension in middle-aged Japanese men. A total of 394 male subjects (age, 53.9±7.9 years; mean±SD) was selected among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as systolic blood pressure (SBP)≥140 mmHg, diastolic blood pressure (DBP)≥90 mmHg, and/or undergoing antihypertensive drug treatment. After adjustment, irrespective of antihypertensive drug treatment, the association between Mt5178C genotype and hypertension was dependent on green tea consumption (P for trend=0.043 and P for trend=0.011, respectively). In particular, among subjects≥50 years old with Mt5178C, excluding those taking antihypertensive drugs, a significant association between green tea consumption and risk of hypertension was observed (P for trend=0.019), and the odds ratio for hypertension was significantly lower in those who consumed≥6 cups of green tea per day than in those who consumed≤1 cup per day (odds ratio=0.167, 95% confidence interval: 0.033-0.832). On the other hand, the association between Mt5178A genotype and hypertension did not depend on green tea consumption. No consistent association between green tea consumption and blood pressure was observed in either genotype. The present results suggest a joint effect for Mt5178C/A polymorphism and green tea consumption on the risk of hypertension in middle-aged Japanese men.

Mitochondrial DNA 5178 C/A polymorphism influences the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.

BACKGROUND: Several genetic polymorphisms have been reported to modify the effects of smoking on serum lipid levels. The objective of this study was to investigate whether longevity-associated mitochondrial DNA 5178 (Mt5178) C/A polymorphism modifies the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese subjects. METHODS: A total of 394 male subjects (age, 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effect of Mt5178 C/A polymorphism and cigarette smoking on the risk of hypo-high-density lipoprotein (HDL) cholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia or hypertriglyceridemia was conducted. RESULTS: For subjects with Mt5178C, the risk of hypo-HDL cholesterolemia increased with the number of cigarettes smoked daily (P for trend = 0.001). On the other hand, the association between Mt5178A genotype and the risk of hypo-HDL cholesterolemia did not appear to depend on the number of cigarettes smoked daily. For those with Mt5178A, the risk of hyper-LDL cholesterolemia or hypertriglyceridemia increased with cigarettes smoked daily (P for trend = 0.017 and P for trend = 0.002, respectively). However, the association between Mt5178C genotype and the risk of hyper-LDL cholesterolemia or hypertriglyceridemia did not depend on the number of cigarettes smoked daily. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modulates the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.

Joint effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on risk of hyper-LDL cholesterolemia in middle-aged Japanese men.

BACKGROUND: Combined effects between mitochondrial DNA 5178 (Mt5178) C/A polymorphism and alcohol consumption on the risk of hypertension or hyperuricemia have been reported. The objective of this study was to investigate whether Mt5178 C/A polymorphism modulates the effects of alcohol consumption on the risk of dyslipidemia. METHODS: A total of 394 male subjects were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effect of Mt5178 polymorphism and alcohol consumption on the risk of dyslipidemia was conducted. RESULTS: For men with Mt5178C, alcohol consumption was significantly and negatively associated with the risk of hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol ≥ 140 mg/dl) (P for trend = 0.015). After adjustment for age, body mass index (BMI), habitual smoking, coffee consumption and use of antihypertensive medicine, the odds ratio (OR) for hyper-LDL cholesterolemia was significantly lower in daily drinkers with Mt5178C than non-drinkers with Mt5178C (OR = 0.360, 95% confidence intervals: 0.153-0.847). A significant and negative association between alcohol consumption and serum LDL cholesterol levels was also observed in Mt5178C genotypic men (P for trend < 0.01). On the other hand, the association between Mt5178A genotype and risk of hyper-LDL cholesterolemia does not appear to depend on alcohol consumption. CONCLUSIONS: For Mt5178C genotypic men, alcohol consumption may reduce the risk of hyper-LDL cholesterolemia.

Combined effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and coffee consumption on the risk of hyper-LDL cholesterolemia in middle-aged Japanese men.

The objective of this study was to investigate whether the mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modifies the effects of coffee consumption on serum lipid levels and the risk of dyslipidemia in middle-aged Japanese men. A total of 397 male subjects (age, 53.9±7.8 years; mean±s.d.) were selected from among individuals visiting the hospital for regular medical check-ups. After adjustment for age, body mass index, habitual alcohol consumption, habitual smoking and use of antihypertensive medication, among subjects who consumed <1 cup of coffee per day, the odds ratio (OR) for hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol > or =140 mg per 100 ml) was significantly lower in those with Mt5178A than in those with Mt5178C (OR=0.378, 95% confidence interval: 0.153-0.919). After adjustment, the association between the Mt5178A genotype and hyper-LDL cholesterolemia depended on coffee consumption (P for trend=0.018). Coffee consumption was positively associated with serum LDL cholesterol levels only in subjects with Mt5178A. However, in subjects with Mt5178C, serum LDL cholesterol level or risk of hyper-LDL cholesterolemia did not seem to depend on coffee consumption. These results suggest that for men with Mt5178A, coffee consumption negates the genetic benefit of lower risk for hyper-LDL cholesterolemia.

Longevity-associated NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modulates the effects of daily alcohol drinking on yearly changes in serum total and LDL cholesterol in Japanese men.

Reduced nicotinamide adenine dinucleotide (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 exert resistance to atherogenic diseases, such as myocardial infarction or cerebrovascular disorders. To investigate whether ND2-237 Leu/Met polymorphism is associated with yearly changes in serum lipid levels, we conducted a longitudinal study of 107 healthy Japanese male subjects. Analysis of covariance revealed that the interaction between the ND2-237 Leu/Met genotypes and habitual drinking was significantly associated with yearly changes in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels (p=0.036 and p=0.006, respectively). In multiple regression analysis, daily drinking was significantly and positively associated with yearly changes in serum LDLC levels in men with ND2-237Met (p=0.026). After adjusting for covariates, yearly changes in serum LDLC levels were significantly lower in non-daily drinkers with ND2-237Met than in those with ND2-237Leu (p=0.047). These results suggest that ND2-237Met has a beneficial impact on yearly changes in serum LDLC in non-daily drinkers but not in daily drinkers.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modulates the effects of coffee consumption on the risk of hypertension in middle-aged Japanese men.

BACKGROUND: Habitual coffee consumption has been reported to lower blood pressure in the Japanese population. The NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity and modifies the effects of alcohol consumption on blood pressure in the Japanese population. The objective of this study was to determine whether this polymorphism also modifies the effects of coffee consumption on blood pressure or the risk of hypertension in middle-aged Japanese men. METHODS: A total of 398 men (mean age +/- standard deviation, 53.8 +/- 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. Hypertension was defined as a systolic blood pressure > or =140 mm Hg, diastolic blood pressure > or =90 mm Hg, or antihypertensive drug treatment. Polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme AluI was performed to determine ND2-237 Leu/Met genotype. RESULTS: In subjects with ND2-237Leu, coffee consumption was significantly and negatively associated with diastolic blood pressure (P = 0.007). The odds ratio (OR) for hypertension was significantly lower in subjects with ND2-237Leu who consumed 2 or 3 cups of coffee per day than in those who consumed less than 1 cup of coffee per day (OR, 0.517; 95% confidence interval [CI], 0.276 to 0.968; P = 0.039). After adjustment, the OR remained significant (OR = 0.399; 95% CI, 0.184 to 0.869; P = 0.020). Moreover, after adjustment, the OR was significantly lower in subjects with ND2-237Leu who consumed more than 4 cups of coffee per day than in those who consumed less than 1 cup of coffee per day (OR, 0.246; 95% CI, 0.062 to 0.975; P = 0.046). However, the association between ND2-237Met genotype and hypertension did not depend on coffee consumption. CONCLUSIONS: The present results suggest that the ND2-237 Leu/Met polymorphism modulates the effects of coffee consumption on hypertension risk in middle-aged Japanese men.

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

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.

NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies the effects of alcohol consumption on risk for hypertension in middle-aged Japanese men.

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.

Longevity-associated NADH dehydrogenase subunit-2 237 Leu/Met polymorphism influences the effects of alcohol consumption on serum uric acid levels in nonobese Japanese men.

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.

Longevity-associated mitochondrial DNA 5178 C/A polymorphism is associated with fasting plasma glucose levels and glucose tolerance in Japanese men.

Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may resist the onset of type 2 diabetes. To investigate whether Mt5178 C/A polymorphism is associated with glucose tolerance, we conducted a cross-sectional study using the 75-g oral glucose tolerance test (OGTT) in which non-diabetic Japanese male subjects were classified into three subgroups by body mass index (BMI): BMI<22 (n=91); 22< or =BMI<25 (n=138); and BMI> or =25 (n=67). The frequency of Mt5178A was significantly lower among 'BMI<22' subjects exhibiting impaired fasting glucose and impaired glucose tolerance than among those with normal glucose tolerance. In the 'BMI<22' group, fasting plasma glucose (FPG) levels and plasma glucose levels at 60 and 120 min after glucose load (OGTT-1h and OGTT-2h, respectively) were significantly lower in the Mt5178A genotype than in the Mt5178C genotype. After adjusting for age, BMI, habitual smoking, habitual drinking and family history of diabetes, FPG levels and OGTT-2h levels were still significantly lower in the Mt5178A genotype than in the Mt5178C genotype. However, after adjusting for covariates, in both the '22< or =BMI<25' and 'BMI> or =25' groups, FPG levels were significantly higher in the Mt5178A genotype than in the Mt5178C genotype. Differences in the effect of alcohol consumption on FPG levels and glucose tolerance between the Mt5178 C/A genotypes were observed. The present results suggest that Mt5178 C/A polymorphism may be associated with FPG levels and glucose tolerance in middle-aged Japanese men.

Longevity-associated NADH dehydrogenase subunit-2 polymorphism and serum electrolyte levels in middle-aged obese Japanese men.

Mitochondrial DNA 5178 cytosine/adenine polymorphism, which is also called NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with Japanese longevity. This polymorphism is widely associated with blood pressure, serum lipid levels, hematological parameters, intraocular pressure, and serum protein fraction levels. However, there have been no reports on the association between ND2-237 Leu/Met polymorphism and serum electrolyte levels. To investigate this relationship, we performed an association study in 321 healthy middle-aged Japanese men. Crude data showed that serum sodium levels and serum chloride levels were significantly lower in men with ND2-237 Met than in those with ND2-237 Leu (P = 0.021 and 0.003, respectively). Cigarette consumption and body mass index were significantly and positively associated with serum chloride levels (P = 0.002 and 0.008, respectively) and hemoglobin levels were significantly and negatively associated with them (P = 0.007) in ND2-237 Leu genotypic men. In men with ND2-237 Met, only hemoglobin levels were significantly and negatively associated with serum chloride levels (P = 0.025). After adjusting for covariates, only in male obese (body mass index> or =25) subjects, serum sodium and chloride levels remained significantly lower, and serum calcium levels appeared to be significantly higher in ND2-237 Met than in ND2-237 Leu (P = 0.013, <0.001, and 0.046, respectively). Longevity-associated NADH dehydrogenase subunit-2 polymorphism may influence serum electrolyte levels in middle-aged obese Japanese men.