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Yoshihiro Kokubo

Publications and source records attributed to Yoshihiro Kokubo.

At least 19 recordsLinked to original sources
PubMed2007

Association of genetic polymorphisms of ACADSB and COMT with human hypertension.

OBJECTIVES: Genetically hypertensive rats provide an excellent model to investigate the genetic mechanisms of hypertension. We previously identified three differentially expressed genes, Acadsb (short/branched chain acyl-CoA dehydrogenase), Comt (catecholamine-O-methyltransferase), and Pnpo (pyridoxine 5'-phosphate oxidase), in hypertensive and normotensive rat kidneys as potential susceptibility genes for rat hypertension. We examined the association of human homologues of these genes with human hypertension. METHODS: We sequenced three genes using samples from 48 or 96 hypertensive patients, identified single nucleotide polymorphisms, and genotyped them in a population-based sample of 1818 Japanese individuals (771 hypertensive individuals and 1047 controls). RESULTS: After adjustments for age, body mass index, present illness (hyperlipidaemia, diabetes mellitus), and lifestyle (smoking, alcohol consumption), multivariate logistic regression analysis revealed that -512A>G in ACADSB was associated with hypertension in women (AA vs AG + GG: odds ratio = 0.70, 95% confidence interval = 0.53-0.94). This single nucleotide polymorphism was in tight linkage disequilibrium with -254G>A. Furthermore, -1187G>C in COMT was associated with hypertension in men (GG vs CG + CC: odds ratio = 0.69, 95% confidence interval = 0.52-0.93) and was in tight linkage disequilibrium with 186C>T. After adjustments described above, -512 A>G and -254G>A in ACADSB were associated with variations in systolic blood pressure. ACADSB was in tight linkage disequilibrium with MGC35392 across a distance of 18.3 kb. COMT was not in linkage disequilibrium with any adjacent genes. Analysis indicated that two haplotypes of COMT were significantly associated with hypertension in men. CONCLUSION: Our study suggests the possible involvement of genetic polymorphisms in ACADSB and COMT in essential hypertension in the Japanese population.

Acyl-CoA Dehydrogenases↗
PubMed2006

Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients.

The dose required for the anticoagulant effect of warfarin exhibits large inter-individual variations. This study sought to determine the contribution of four genes, vitamin K epoxide reductase (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU), and cytochrome P450 2C9 (CYP2C9) to the warfarin maintenance dose required in Japanese patients following ischemic stroke. We recruited 93 patients on stable anticoagulation with a target International Normalized Ratio (INR) of 1.6-2.6. We genotyped eleven representative single nucleotide polymorphisms (SNPs) in the three genes involved in vitamin K cycle and the 42613A>C SNP in CYP2C9, known as CYP2C93, and then examined an association of these genotypes with warfarin maintenance doses (mean+/-SD=2.96+/-1.06 mg/day). We found an association of effective warfarin dose with the -1639G>A (p=0.004) and 3730G>A genotypes (p=0.006) in VKORC1, the 8016G>A genotype in GGCX (p=0.022), and the 42613A>C genotype in CYP2C9 (p=0.015). The model using the multiple regression analysis including age, sex, weight, and three genetic polymorphisms accounted for 33.3% of total variations in warfarin dose. The contribution to inter-individual variation in warfarin dose was 5.9% for VKORC1 -1639G>A, 5.2% for CYP2C9 42613A>C, and 4.6% for GGCX 8016G>A. In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients.

Aged↗
PubMed2006

Extensive genetic analysis of 10 candidate genes for hypertension in Japanese.

The identification of genes that contribute to essential hypertension has been hampered because of a lack of statistical power and problems with multiple testing. In the present study, we performed association analyses between the 161 single nucleotide polymorphisms of 10 candidate genes and hypertension in a Japanese population recruited from the Suita Study (n=3654). We found that 5 polymorphisms in the 3 genes (SLC9A2, UMOD, and ELN) were associated with hypertension status, and 4 of these 5 polymorphisms were also associated with blood pressure values with a classical criterion of P<0.05. However, when a Bonferroni correction for multiple testing was applied, none of the polymorphisms were associated with blood pressure levels. We also performed association analyses between these 5 polymorphisms and intermediate phenotypes corresponding with the functions of candidate genes, including the renin/aldosterone profile, plasma uric acid levels, and pulse wave velocity. The ELN 3'-untranslated region (-/A) polymorphism was found to significantly affect pulse wave velocity, an indicator of arterial stiffness. Associations of the ELN 3'-untranslated region (-/A) polymorphism with hypertension and pulse wave velocity were reconfirmed in another set of the study population. Thus, ELN seems to contribute to blood pressure regulation by affecting arterial stiffness in Japanese.

Adult↗
PubMed2006

A low level of C-reactive protein in Japanese adults and its association with cardiovascular risk factors: the Japan NCVC-Collaborative Inflammation Cohort (JNIC) study.

High-sensitivity C-reactive protein (hs-CRP) levels vary remarkably by race and ethnic group. We examined hs-CRP levels and their association with cardiovascular risk factors in the Japanese general population. The Japan National Cardiovascular Center (NCVC)-collaborative Inflammation Cohort (JNIC) Study recruited 5213 men and 7071 women aged > or = 40 years from seven communities in Japan during 2002-2004. hs-CRP was measured using nephelometry calibrated with CRM 470, the international plasma protein reference material. Traditional cardiovascular risk factors and their aggregation were studied in multivariate logistic models, stratified by overweight status. Median hs-CRP levels in men and women were 0.60 and 0.45 mg/L, respectively. The percentage of subjects with hs-CRP levels < 1.0, 1.0-3.0, and > 3.0 mg/L was 67.4%, 22.0%, and 10.6% in men, respectively, and 76.3%, 16.7%, and 7.0% in women. hs-CRP levels showed significant linear associations with traditional risk factors. Overweight, hypertension, dyslipidemia (men only), smoking (men only), and diabetes (women only) contributed significantly to elevated hs-CRP levels. Overweight individuals with hypertension, dyslipidemia, and diabetes had a high prevalence of elevated hs-CRP levels in both sexes. Japanese adults have very low hs-CRP levels. An aggregation of metabolic risk factors is associated with elevated hs-CRP levels among overweight individuals, particularly in women.

Aged↗
PubMed2006

Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population.

INTRODUCTION: Thrombomodulin (TM) is an essential cofactor in protein C activation by thrombin. Here, we evaluated the contribution of genetic variations in the TM gene to soluble TM (sTM) level and deep vein thrombosis (DVT) in Japanese. PATIENTS AND METHODS: We sequenced the TM putative promoter, exon, and 3'-untranslated region in DVT patients (n=118). Among 17 genetic variations we identified, two missense mutations (R385K, D468Y) and three common single nucleotide polymorphisms (-202G>A, 2487A>T, 2729A>C) were genotyped in a general population of 2247 subjects (1032 men and 1215 women) whose sTM levels were measured. We then compared the frequency of these mutations in DVT patients with that in the age, body mass index-adjusted population-based controls. RESULTS: We identified one neutral mutation (H381) and three missense mutations (R385K; n=2, A455V; n=53 heterozygous, n=14 homozygous, D468Y; n=2) of TM in the DVT patients. Age-adjusted mean values of sTM were lower in C-allele carriers of 2729A>C than in noncarriers in the Japanese general population (women: 16.7+/-0.3 U/ml vs. 17.9+/-0.2 U/ml, p<0.01, men: 19.4+/-0.3 U/ml vs. 20.4+/-0.3 U/ml, p=0.03). Additionally, the CC genotype of this mutation was more common in the male DVT patients than in the male individuals of the general population (odds ratio=2.76, 95% confidence interval=1.14-6.67; p=0.02). This mutation was in linkage disequilibrium (r-square>0.9) with A455V mutation. CONCLUSIONS: TM mutations, especially those with a haplotype consisting of 2729A>C and A455V missense mutation, affect sTM levels, and may be associated with DVT in Japanese.

3' Untranslated Regions↗
PubMed2006

Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I.

BACKGROUND: Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk. METHODS AND RESULTS: To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41,578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990-1992 to 2001. After 477,325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]). CONCLUSIONS: Compared with a modest fish intake of once a week or &20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.

Adult↗
PubMed2006

Assessment of genetic effects of polymorphisms in the MCP-1 gene on serum MCP-1 levels and myocardial infarction in Japanese.

BACKGROUND: Recently, the Framingham Heart Study reported that genetic variations in CCL2 influence serum levels of monocyte chemoattractant protein-1 (MCP-1) and the incidence of myocardial infarction (MI). The purpose of the present study was to investigate the possible involvement of CCL2 in the pathogenesis of atherosclerosis and MI in Japanese. METHODS AND RESULTS: Multiple regression analysis indicated that the MCP-1 levels were significantly influenced by various factors including age, body mass index, smoking, alcohol intake, high density lipoprotein-cholesterol, and systolic blood pressure. Moreover, the serum MCP-1 level was significantly correlated with intima - media thickness (p < 0.0001). However, this association disappeared when other clinical confounding factors were included in the analyses. Comprehensive analysis of common polymorphisms of CCL2 in a large community-based population and in subjects with MI found that the A(-2138)T polymorphism affected the serum MCP-1 level in a subgroup of subjects 65 years and older. However, no significant differences in the frequencies of any of the polymorphisms or haplotypes were found between subjects with and without MI. None of the polymorphisms in CCL2 affected carotid atherosclerosis. CONCLUSIONS: The serum MCP-1 level was a good surrogate marker of atherosclerosis in the present study population. Although genetic variations in CCL2 may have some influence on MCP-1 production, their influence does not seem to contribute appreciably to atherosclerosis in Japanese. The present results did not support the recently published findings from the Framingham Heart Study. The discrepancy between the 2 studies may be related to differences in confounding factors that contribute to MCP-1 levels and in the haplotype structure of the 2 populations.

Aged↗
PubMed2006

Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2006

Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.

We previously selected a group of hypertension candidate genes by a key word search using the OMIM database of NCBI and validated 525 coding single nucleotide polymorphisms (SNPs) in 179 hypertension candidate genes by DNA sequencing in a Japanese population. In the present study, we examined the association between 61 non-synonymous SNPs and blood pressure variations and hypertension. We used DNA samples taken from 1,880 subjects in the Suita study, a population-based study using randomly selected subjects. Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations. Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension. Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension. Thus, our study suggests that these five genes were susceptibility genes for essential hypertension in this Japanese population.

Aged↗
PubMed2006

Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population.

gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K-dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G>A change leads to the substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.

Aged↗
PubMed2006

Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K196E mutation.

There is mounting evidence that mutations associated with a given disease arise with different frequencies among ethnic groups, thus ethnicity-specific studies are needed to identify causative mutations and properly assess risk. In particular, ethnic differences in the genetic background of thrombophilia have been reported. We recently conducted a large-scale analysis of the plasma activities of proteins C, S, antithrombin, and plasminogen within the Japanese general population. We found age- and sex-related differences and estimated the prevalence of deficiencies of protein C (0.13%), antithrombin (0.15%), protein S (1.12%), and plasminogen (4.29%). We also evaluated the genetic contribution to deep vein thrombosis and found that protein S mutation K196E is a genetic risk factor in the Japanese population. We estimated allele frequency to be 0.009, suggesting that 1 of 12,000 Japanese may be homozygous for the E allele, thus possibly as many as 10,000 individuals. Accordingly, a substantial proportion of the Japanese population carries the protein S E allele and is at risk of developing deep vein thrombosis. Given the frequency of this mutation and its strong correlation with deep vein thrombosis, it may be valuable to conduct a large-scale screening for this allele and advise concerned persons to avoid environmental risk factors known to be associated with deep vein thrombosis.

Age Factors↗
PubMed2005

Hypertension susceptibility genes on chromosome 2p24-p25 in a general Japanese population.

BACKGROUND: Genome-wide scans from Italy and China suggest a hypertension-susceptible locus between D2S2278 (nucleotides 11,245,080 - 11,245,358) and D2S168 (nucleotides 11,467,214 - 11,467,422) on chromosome 2. METHODS: We performed a large association study of polymorphisms in this region with blood pressure modulation in a Japanese general population. Forty-seven polymorphisms in 14 genes between nucleotide 8,845,292 and nucleotide 11,946,689, which contains D2S2278 and D2S168, were genotyped in 1880 individuals, 796 of whom were hypertensive and 1084 normotensive. RESULTS: Multivariate logistic regression analysis with adjustment for age, body mass index, presence of hyperlipidemia, diabetes mellitus, and current smoking and drinking revealed that one single nucleotide polymorphism (SNP), IMS-JST126186, in HPCAL1 (hippocalcin-like 1) in women and two SNPs, IMS-JST149391 and IMS-JST149390, in GREB1 (gene regulated by estrogen in breast cancer 1) in men were significantly associated with both prevalence of hypertension and blood pressure levels. To examine the role of GREB1 in more detail, we identified 38 additional genetic variations in GREB1 by direct sequencing, and eight polymorphisms were genotyped. One SNP, 45718A>G, was significantly associated with hypertension and blood pressure level in men, and this SNP was in linkage disequilibrium with a SNP present at the 3' splice site of intron 11. CONCLUSION: Our study suggests that GREB1 and HPCAL1 are candidate hypertension-susceptibility genes in the Japanese general population and supports previous studies that also identified hypertension-related loci in this narrow region.

Adult↗
PubMed2005

Genetic variations of regulator of G-protein signaling 2 in hypertensive patients and in the general population.

OBJECTIVES: Mice deficient in the regulator of G-protein signaling 2 (RGS2) exhibit a strong hypertensive phenotype. We studied whether genetic variations in RGS2 are implicated in hypertension or other phenotypes in Japanese hypertensive individuals and the general population. METHODS: We sequenced all exons of RGS2 and the promoter region in 953 and 48 hypertensive individuals, respectively. Genotyping by the TaqMan polymerase chain reaction method was performed for six missense or frameshift mutations and common single nucleotide polymorphisms in the general population, with a sample size of 1872 individuals (862 men and 1011 women). RESULTS: We identified five novel missense mutations (Q2L; n = 2, Q2R; n = 1, M5V; n = 1, R44H; n = 2, Q78H; n = 1) and one novel frameshift mutation (1925-1926insT; n = 2) in a heterozygous state, in addition to 33 variations including five common single nucleotide polymorphisms. Six missense/frameshift mutations and three common single nucleotide polymorphisms (-638A > G, 1026T > A, 1891-1892delTC) were successfully genotyped in the general population. Mutations Q2L (n = 2), M5V (n = 1), and 1925-1926insT (n = 2) were only identified in hypertensive subjects. Six out of seven individuals with the R44H mutation, which occurs in the amphipathic alpha-helical domain of RGS2, had hypertension. The results showed a significant association of two common single nucleotide polymorphisms, 1026T > A [TT versus TA + AA: odds ratio (OR) 1.33; 95% confidence interval (CI) 1.02-1.74; P = 0.035] and 1891-1892delTC (I: insertion allele, D: deletion allele, II versus ID + DD: OR 1.47; 95% CI 1.09-1.97; P = 0.012), with hypertension in women by multivariate logistic regression analysis. CONCLUSION: Our results suggest that genetic variations in RGS2 contribute partly to the hypertensive phenotype.

Aged↗
PubMed2005

FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay.

A plasma metalloprotease, ADAMTS13, cleaves von Willebrand factor (VWF) multimers and downregulates their activity in platelet aggregation. Functional ADAMTS13 deficiency leads to the accumulation of hyperactive large VWF multimers, inducing a life-threatening disease, thrombotic thrombocytopenic purpura (TTP). Although measuring ADAMTS13 activity is important in TTP diagnosis, existing methods require time and skill. Here, we report a fluorescence resonance energy transfer (FRET) assay for ADAMTS13 activity. We developed a synthetic 73-amino-acid peptide, FRETS-VWF73. Cleavage of this substrate between two modified residues relieves the fluorescence quenching in the intact peptide. Incubation of FRETS-VWF73 with normal human plasma quantitatively increased fluorescence over time, while ADAMTS13-deficient plasma had no effect. Quantitative analysis could be achieved within a 1-h period using a 96-well format in commercial plate readers with common filters. The FRETS-VWF73 assay will be useful for the characterization of thrombotic microangiopathies like TTP and may clarify the importance of ADAMTS13 activity as a predictive marker for various thrombotic diseases.

ADAM Proteins↗
PubMed2005

Validation of the association between the gene encoding 5-lipoxygenase-activating protein and myocardial infarction in a Japanese population.

BACKGROUND: Recently, the 5-lipoxygenase activating protein gene (ALOX5AP) was reported to confer a risk of myocardial infarction (MI) and stroke, independent of conventional risk factors. The purpose of the present study was to validate those findings in a Japanese population. METHODS AND RESULTS: The study population consisted of 1,875 subjects (males 871, females 1,004) recruited from the Suita study (control group) and 353 subjects (males 306, females 47) with MI. The promoter, all of the exons, and 3'UTR regions of ALOX5AP were sequenced in 96 subjects, and 8 polymorphisms were found. There were significant differences in the frequencies of the haplotypes constructed from the 2 SNPs (A162C and T8733A) between the control and MI groups. Multiple logistic analysis indicated that the homozygous genotype of the (CA) haplotype was significantly associated with a reduced risk for MI. CONCLUSION: The hypothesis that ALOX5AP contributes to susceptibility for MI was validated in a Japanese population.

3' Untranslated Regions↗
PubMed2005

Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population--the Suita Study.

BACKGROUND: Reproducibility of results is important for the validity of genetic association studies. Recently, 3 functional polymorphisms, G(-930)A in CYBA, T481S in CLCNKB, and E65K in KCNMB1, were reported to be associated with blood pressure (BP) status and the aim of this study was to confirm those findings using a large cohort representing the general Japanese population. METHODS AND RESULTS: The study population consisted of 3,652 subjects recruited from the Suita study as representative of the general population in Japan. The genotypes of the 3 polymorphisms were determined by the TaqMan method. Logistic analysis indicated that the CYBA/G(-930)A polymorphism was associated with hypertension in male subjects. In the male population, the odds ratio of the GG genotype over GA + AA was 1.27 (95% confidence interval 1.01-1.57, p=0.034). Moreover, residuals of systolic and diastolic BP values were significantly higher in subjects with the GG genotype than in those with the GA or AA genotype (p=0.0007). However, such significant effects of the genotype on BP status were not observed in the female population. The significance of the CLCNKB/T481S and KCNMB1/E65K polymorphisms were not replicated in the present study. CONCLUSION: The significance of the G(-930)A polymorphism of CYBA was confirmed in the present study with adequate statistical power, which strengthens the hypothesis that this polymorphism is important in the pathogenesis of hypertension and confers susceptibility.

Aged↗
PubMed2005

Single nucleotide polymorphisms in the interleukin-6 gene associated with blood pressure and atherosclerosis in a Japanese general population.

It is known that increased plasma levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with atherosclerosis and myocardial infarction. The aim of this study was to reveal the contribution of the single nucleotide polymorphisms (SNPs) of the IL-6 gene on the blood pressure regulation and progression of atherosclerosis in a general Japanese population. In order to evaluate the potential implications of genetic variability of the IL-6 gene, we explored eight SNPs by direct sequencing for the entire coding region and the promoter region in the IL-6 gene and genotyped two SNPs, -636G > C in the promoter region and 1691C > G in intron 3, for a total of 2,421 Japanese subjects (1,162 men and 1,259 women). As a consequence, -636 G > C was significantly associated with systolic blood pressure (SBP) and carotid intima-media thickness (IMT) in women, and 1691C > G showed a relationship with SBP and carotid IMT in men after adjustment for all confounding factors. Although neither SNP had a significant correlation to the prevalence of hypertension, the haplotype frequency analysis indicated that the number of hypertensive men with a G allele at both -636 and 1691 was significantly greater than the number of nonhypertensive men with this combination. Thus, these two SNPs in the promoter region and intron 3 of the IL-6 gene might play a role in the blood pressure regulation and progression of atherosclerosis in the Japanese.

Aged↗