Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure in the Japanese population

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.

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

“…The frequency of the Mt5178A genotype, a genetic marker of mitochondrial haplogroup D, is significantly higher in Japanese centenarians than in the general population (Alexe et al 2007;Tanaka et al 1998) and it is reported that individuals with Mt5178A (mitochondrial haplogroup D) are less susceptible to lifestyle-related adult-onset diseases, for example hypertension (Kokaze et al 2007), diabetes (Wang et al 2001), metabolic syndrome ), myocardial infarction (Mukae et al 2003;Takagi et al 2004), and cerebrovascular diseases (Ohkubo et al 2002), than those with Mt5178C. Mt5178 C/A polymorphism is, moreover, also reported to be associated with blood pressure (Kokaze et al 2004a(Kokaze et al , 2007, serum lipid levels (Kokaze et al 2001(Kokaze et al , 2003a, fasting plasma glucose levels and glucose tolerance (Kokaze et al 2005a), serum uric acid levels (Kokaze et al 2006), intraocular pressure (Kokaze et al 2004b), hematological data (Kokaze et al 2005b), and serum protein fraction levels (Kokaze et al 2002(Kokaze et al , 2003b, and its interaction with smoking habits is associated with serum triglyceride levels (Kokaze et al 2003a), intraocular pressure (Kokaze et al 2004b), red blood cell counts (Kokaze et al 2005b), and serum protein fraction levels (Kokaze et al 2003b). As far as we are aware, however, no information is available about the relationship between Mt5178 C/A polymorphism and respiratory function or about its interaction with smoking habits in respiratory function.…”

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

“…14 This polymorphism is reportedly associated with serum lipid levels 15 and fasting plasma glucose levels. 16 Moreover, the Mt5178 C/A polymorphism modulates the effects of alcohol consumption on blood pressure, 17 risk of hypertension, 10 serum triglyceride levels, 18 yearly changes in serum low-density lipoprotein (LDL) cholesterol levels 19 and serum uric acid levels. 20 Previous studies have also reported the combined effects of the Mt5178 C/A polymorphism and coffee consumption on the risk of hypertension 21 or abnormal glucose tolerance 22 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

“…ND2-237Met may exert antiatherogenic effects (Kokaze et al 2001;Matsunaga et al 2001). We previously reported that this polymorphism may be associated with blood pressure (Kokaze et al 2004), serum lipid levels (Kokaze et al 2001(Kokaze et al , 2003, and FPG levels and glucose Frequency of subjects with SUA levels ‡6.5 mg/dl b Frequency of subjects with SUA levels ‡7.0 mg/dl c OR adjusted for age, body mass index, habitual smoking, systolic blood pressure, diastolic blood pressure, logarithm-transformed serum triglyceride levels, logarithm-transformed serum c-GTP levels, and serum creatinine levels *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.001 Serum uric acid (SUA): mean ± SD. Adjusted for age, BMI, habitual smoking, systolic blood pressure, diastolic blood pressure, logarithm-transformed serum triglyceride levels, logarithm-transformed serum c-GTP levels, and serum creatinine levels.…”

“…Determination of blood chemical [SUA levels, serum total cholesterol levels, serum high-density lipoprotein (HDL) cholesterol levels, serum TG levels, serum gamma-glutamyltranspeptidase (c-GTP) levels, and serum creatinine levels] and physical [weight, height, systolic blood pressure (SBP), and diastolic blood pressure (DBP)] data was conducted as described previously (Kokaze et al 2001(Kokaze et al , 2004. Briefly, venous blood was drawn after a minimum fasting period of 12 h. The body mass index (BMI) was defined as the ratio of subject weight (kg) to the square of subject height (m).…”

“…Moreover, genetic epidemiological research has shown that alcohol dehydrogenase 2 (ADH2) genotype (Hashimoto et al 2002) or endothelial constitutive nitric oxide synthase (ecNOS) genotype (Nishio et al 2005) influences the effects of alcohol consumption on serum uric acid (SUA) levels in the Japanese male population. We previously reported the interaction between ND2-237 Leu/Met polymorphism and daily alcohol intake on blood pressure (Kokaze et al 2004), serum triglyceride (TG) levels (Kokaze et al 2003), and fasting plasma glucose (FPG) levels and response to 75-g oral glucose tolerance tests (75-g-OGTT) (Kokaze et al 2005) in healthy Japanese men. To our knowledge, there have been no reports regarding the association between longevityassociated ND2-237 Leu/Met polymorphism and SUA levels, or the effect of ND2-237 Leu/Met polymorphism and drinking frequency on SUA levels.…”