Community-dwelling Japanese Individuals Research Articles

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relationships of 22 candidate gene polymorphisms with the prevalence of hypertension and with blood pressure (BP) in a 6-year population-based longitudinal cohort study and observed significant relationships of three polymorphisms of SORBS1, GCK and WISP1 with hypertension. The 2233 subjects (1106 women, 1127 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in the sitting position for at least 15 min. Genotypes for the 682A --> G (Thr228Ala) polymorphism of SORBS1, the -30G --> A polymorphism of GCK and the 2364A --> G polymorphism of WISP1 were determined by melting curve analysis. Longitudinal analysis with a generalized estimating equation revealed that the polymorphisms of SORBS1 and GCK and that of WISP1 were significantly associated with the prevalence of hypertension in women and men, respectively. Longitudinal analysis with a mixed-effect model revealed that the polymorphism of SORBS1 was significantly related to diastolic BP in women and that those of GCK and WISP1 were significantly related to both systolic and diastolic BP in women and men, respectively. These results suggest that SORBS1 and GCK are susceptibility loci for hypertension in Japanese women and that WISP1 is such a locus in men.

Proposed Criteria for Metabolic Syndrome in Japanese Based on Prospective Evidence

The current criteria of metabolic syndrome (MetS) are not based on evidence derived from prospective studies on cardiovascular disease (CVD). In a 14-year follow-up study of 2452 community-dwelling Japanese individuals aged >or=40 years, we examined which of the MetS criteria are most predictive for the development of CVD. During the follow-up, 246 first-ever CVD events occurred. An optimal cutoff point of waist circumference for predicting CVD was 90 cm in men (age-adjusted hazard ratio=1.81; 95% CI, 1.19 to 2.74; P=0.005) and 80 cm in women (age-adjusted hazard ratio=1.46; 95% CI, 0.99 to 2.16; P=0.05). A comparison of MetS criteria showed that the modified Japanese criteria using this cutoff point instead of the original definition were the strongest predictor of CVD events in both sexes (men: age-adjusted hazard ratio=2.58; 95% CI, 1.65 to 4.02; P<0.001; women: age-adjusted hazard ratio=2.39; 95% CI, 1.65 to 3.48; P<0.001). These observations remained robust even after adjustment for other confounding factors. According to this criteria set, only in the presence of central obesity, the hazard ratios for future CVD increased significantly as the number of MetS components increased, and a significant relationship was identified from 2 or more MetS components compared with individuals who had no MetS component. Our findings suggest that the optimal cutoff point of waist circumference is 90 cm in men and 80 cm in women and that the modified Japanese criteria of MetS with this cutoff point as an essential component better predict CVD in the general Japanese population.

Association of the genetic variants of APOA5 and PRKCH with hypertension in community-dwelling Japanese individuals

Hypertension is a complex multifactorial disorder that is thought to result from the interaction between genetic background and environmental factors. Although various loci and genes have been implicated in the predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relation of five candidate gene polymorphisms to blood pressure (BP) and the prevalence of hypertension in an 8-year population-based longitudinal cohort study. The 2267 subjects (1128 women, 1139 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured after subjects had rested in a sitting position for at least 15 min. Genotypes for the -765G↷C polymorphism of PTGS2 and the 67G↷A (Ala23Thr) polymorphism of CCL11 were determined using a fluorescence-based allele-specific DNA primer assay system, and those of the 1444T↷C (3'-UTR) polymorphism of CRP, the -1131T↷C polymorphism of APOA5 and the 1425G↷A (Val374Ile) polymorphism of PRKCH using melting curve analysis. Longitudinal analysis of the relation between systolic or diastolic BP and the five polymorphisms with a mixed-effect model revealed that the polymorphism of CRP was significantly related to systolic BP in all subjects, that of APOA5 to systolic BP in men, and that of PRKCH to diastolic BP in women. Longitudinal analysis of the relation between the prevalence of hypertension and the five polymorphisms with a generalized estimating equation revealed that the CRP, APOA5 and CCL11 polymorphisms were significantly related to the prevalence of hypertension in men, the PTGS2 polymorphism to its prevalence in all subjects, and the PRKCH polymorphism to its prevalence in all subjects and in women. The APOA5 and PRKCH polymorphisms were thus associated with both BP and the prevalence of hypertension in men and women, respectively. These results suggest that the APOA5 and PRKCH polymorphisms are determinants of BP and the development of hypertension in Japanese men and women, respectively.

Impact of Metabolic Syndrome on the Development of Cardiovascular Disease in a General Japanese Population

The metabolic syndrome (MetS) is associated with an increased risk of cardiovascular disease (CVD) events in general populations. However, well-designed prospective studies in Asian populations are very limited. We prospectively evaluated a total of 2452 community-dwelling Japanese individuals aged 40 years or older from 1988 to 2002 and examined the effects of MetS defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria on incident CVD. The prevalence of the MetS was 21% in men and 30% in women at baseline. During the follow up, 307 CVD events occurred. Compared with those without MetS, the age-adjusted incidence of CVD (per 1000 person-years) was significantly higher in subjects with the MetS in both men (21.8 versus 11.6, P<0.01) and women (12.9 versus 6.5, P<0.01). The risk of CVD events was significantly higher even after adjusting for the following confounding factors: age, proteinuria, electrocardiographic abnormalities, serum total cholesterol, smoking habits, alcohol intake, and regular exercise (hazard ratio, 1.86; 95% CI, 1.32 to 2.62 in men and hazard ratio, 1.70; 95% CI, 1.22 to 2.36 in women). The risk of incident CVD was found to increase with the number of components of MetS and became significantly predictive when the number of components reached 3. Similar associations were also observed when CVD was divided into coronary heart disease and stroke. Our findings suggest that MetS is a significant risk factor for the development of CVD in the Japanese middle-aged population.

Association of gene polymorphisms with blood pressure and the prevalence of hypertension in community-dwelling Japanese individuals

Hypertension is a complex multifactorial disorder that is thought to result from an interaction between genetic background and environmental factors. Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We examined the relations of nine candidate gene polymorphisms to blood pressure (BP) and the prevalence of hypertension in a population-based study. The 2238 subjects (1110 women, 1128 men) were aged 40 to 79 years and were randomly recruited for a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in a sitting position for at least 15 min. Genotypes for the 160C-->T (Arg54Trp) polymorphism of QPCT, the C-->T (Pro198Leu) polymorphism of GPX1, the 137,346T-->C polymorphism of FYN, the -344C-->T polymorphism of CYP11B2, and the A-->G (Ser49Gly) polymorphism of ADRB1 were determined with a fluorescence-based allele-specific DNA primer assay system; those for the A-->G polymorphism of CNR2, the I/D (22,375delAC) polymorphism of CAV1, and the -1213T-->C polymorphism of ESR2 by melting curve analysis, and that for the (GT)n polymorphism of COL1A2 were determined by DNA fragment analysis. The polymorphism of FYN was associated with systolic and diastolic BP in women. In men, polymorphisms of CNR2, QPCT, GPX1, COL1A2, CYP11B2, and ESR2 were associated with systolic and diastolic BP, those of CAV1 and FYN with systolic BP, and that of ADRB1 with diastolic BP. The polymorphisms of QPCT and CYP11B2 were also associated with the prevalence of hypertension in men. These results suggest that polymorphisms of QPCT and CYP11B2 are determinants of BP and the development of hypertension in Japanese men.

Medical costs of patients with hypertension and/or diabetes: a 10-year follow-up study of National Health Insurance in Shiga, Japan

A cohort study investigating medical costs associated with the combination of hypertension and diabetes was conducted. The participants included 4535 community-dwelling Japanese individuals, aged 40-69 years, who were classified into the following four categories: 'Neither hypertension nor diabetes', 'Hypertension alone', 'Diabetes alone' or 'Both hypertension and diabetes'. Medical costs per person per month were compared among the four categories. Of the study population, 1.3% had both hypertension and diabetes. During the 10-year follow-up period, participants with both hypertension and diabetes incurred higher medical costs, as compared with those without hypertension, diabetes or their combination, even after adjustment for other confounding factors.

Association of polymorphisms in forkhead box C2 and perilipin genes with bone mineral density in community-dwelling Japanese individuals

Evidence suggests the existence of a close relation between lipid metabolism and bone remodeling. We hypothesized that polymorphisms of genes that play a role in lipid metabolism, such as those for forkhead box C2 (FOXC2) and perilipin (PLIN), might affect bone mineral density (BMD). We thus examined the possible relationships between a -512C --> T polymorphism of FOXC2 and a 1243C --> T polymorphism of PLIN to BMD in community-dwelling Japanese women and men. The subjects (1129 men, 1114 women for FOXC2; 1122 men, 1112 women for PLIN) were aged 40 to 79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. Genotypes for FOXC2 and PLIN were determined with a fluorescence-based allele-specific DNA primer assay system. The -512C --> T polymorphism of FOXC2 was associated with BMD for the distal and proximal radius in men and in premenopausal women as well as with BMD for the distal radius and total body in postmenopausal women, with the T allele being related to reduced BMD. The 1243C --> T polymorphism of PLIN was associated with BMD for the total body, lumbar spine, femoral neck, and trochanter in men, with the C allele being related to reduced BMD. This polymorphism of PLIN was not associated with BMD in all women. These results suggest that FOXC2 is a susceptibility locus for reduced BMD in Japanese men and women, and that PLIN constitutes such a locus in Japanese men.

Characteristics of the insulin resistance syndrome in a Japanese population. The Jichi Medical School Cohort Study.

We investigated the relationships between hyperinsulinemia (a major indicator of the insulin resistance syndrome), blood pressure, dyslipidemia, and coagulation factors in 2606 community-dwelling Japanese individuals as part of the Jichi Medical School Cohort Study. An age-related decrease of the fasting insulin level was found in men but not in women. Body mass index, systolic and diastolic blood pressure, triglyceride and fasting glucose levels, and factor VII activity all increased in both sexes as the insulin level became higher, while the HDL cholesterol level decreased. In addition, total cholesterol and LDL cholesterol levels increased as the insulin level became higher and lipoprotein(a) levels decreased in the men. Fibrinogen levels were not related to the insulin level in either sex. Multiple logistic regression analysis revealed that fasting insulin levels were positively correlated with body mass index and fasting glucose and factor VII activity levels, whereas they were negatively correlated with HDL cholesterol in both sexes. In addition, fasting insulin levels were positively correlated with LDL cholesterol levels in men and with triglyceride levels in women. Our results indicate that hyperinsulinemia is associated with high factor VII activity in a general Japanese population as well as with high blood pressure and dyslipidemia. The accumulation of these cardiovascular risk factors in hyperinsulinemic subjects appears to contribute to cardiovascular events in the Japanese as well as in westerners.