As one approach to exploring whether the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is associated with atherosclerosis, we genotyped 461 healthy Japanese individuals and studied the relationship of mt5178 A/C genotypes to serum lipid levels. Blood specimens were obtained after at least a 12-h fasting period from the subjects. The mt5178 A/C was genotyped by the polymerase chain reaction/restriction fragment length polymorphism method. The relative frequency of mt5178 A was 41.6% (192/461) and of mt5178 C was 58.4% (269/461). After adjustments for age and body mass index, the high-density lipoprotein cholesterol concentration in males carrying mt5178 A was significantly higher than that in males carrying mt5178 C ( P=0.026). The tryglyceride (TG) concentration in females carrying mt5178 A was significantly lower than that in females carrying mt5178 C ( P=0.012). This difference in the TG level between the two genotypes was more evident in postmenopausal females than in premenopausal females. Mt5178 A seems to have an antiatherogenic effect. This is the first genetic epidemiological report on the association of mt5178 A/C polymorphism with serum lipid levels in the Japanese population.

No abstract

It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism, also called NADH dehydrogenase subunit 2-237 methionine/ leucine (ND2-237 Met/Leu) polymorphism, may be associated with longevity in Japanese individuals, and that the mt5178A genotype may have an antiatherogenic influence. To determine whether mt5178 A/C polymorphism influences blood pressure, we genotyped 412 healthy Japanese individuals and performed a crosssectional study investigating the relationship between genotype and blood pressure. In women with mt5178A, the mean diastolic blood pressure was higher than in those with mt5178C by 3.2 mmHg (P ¼ 0.040). In men, no statistically significant difference in systolic or diastolic blood pressure was observed between mt5178 A/C genotypes. However, a significant correlation between mt5178 A/C genotypes and the effects of habitual drinking on blood pressure was found. After adjustment for several factors, in men carrying mt5178C, both systolic and diastolic blood pressure were significantly higher in daily drinkers than in occasional (P ¼ 0.002 and 0.002, respectively) as well as nondrinkers (Po0.001 and 0.001, respectively), whereas in men carrying mt5178A, no significant differences in blood pressure were detected, irrespective of alcohol consumption. These results suggest that mt5178 A/C ( ¼ ND2-237 Met/Leu) polymorphism may influence both diastolic blood pressure in Japanese women and the blood-pressureincreasing effect of drinking in Japanese men.

No abstract

No abstract

BackgroundHabitual 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.MethodsA 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 ≥140 mm Hg, diastolic blood pressure ≥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.ResultsIn 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.ConclusionsThe present results suggest that the ND2-237 Leu/Met polymorphism modulates the effects of coffee consumption on hypertension risk 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 o1 cup of coffee per day, the odds ratio (OR) for hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol X140 mg per 100 ml) was significantly lower in those with Mt5178A than in those with Mt5178C (OR¼0.378, 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 trend¼0.018). 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.

BackgroundMitochondrial 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.MethodsA 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.ResultsFor 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).ConclusionsThese 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.