Effects of Angiotensin II Type 1 Receptor Gene Polymorphisms on Insulin Resistance in a Japanese General Population: The Tanno-Sobetsu Study

Akasaka, Hiroshi; Katsuya, Tomohiro; Saitoh, Shigeyuki; Sugimoto, Ken; Fu, Ying-Shuang; Takagi, Satoru; Ohnishi, Hirofumi; Rakugi, Hiromi; Ura, Nobuyuki; Shimamoto, Kazuaki; Ogihara, Toshio

doi:10.1291/hypres.29.961

Cited by 25 publications

(23 citation statements)

References 40 publications

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“…AGT polymorphisms encoding the M235T amino acid substitution, as well as the AT1R polymorphism1166A/C, were determined by amplification with biotinylated primers and hybridization to immobilized sequence-specific oligonucleotides as previously described. 17 …”

Section: Genotypingmentioning

confidence: 99%

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

et al. 2011

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The renin-angiotensin system (RAS) adversely affects stroke and cardiovascular disease; polymorphisms in genes involved in this system are associated with cardiovascular disease. The aim of the present study was to confirm the genetic risk of these polymorphisms for stroke and cardiovascular events in a cohort study of 515 hypertensive patients in Japan (follow-up period 90.6±30.2 months). The insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE), the M235T amino acid change in angiotensinogen, and the A1166C polymorphism in angiotensin II type 1 receptor were determined by TaqMan PCR. In Kaplan-Meier analyses, the ACE I/D polymorphism was a risk factor for cerebro-cardiovascular events, especially cardiovascular events (Po0.0001), and the M235T mutation was a risk factor for cardiovascular events (Po0.0105). The cumulative rates of cerebro-cardiovascular end points for the ACE polymorphism were 10.6, 16.4 and 42.2% for the II (n¼207), ID (n¼244) and DD (n¼64) genotype carriers, respectively (Po0.0001). Cox's proportional hazard models revealed that the ACE DD genotype was a risk factor for cerebro-cardiovascular and cardiovascular events (after adjusting for common risk factors), anti-hypertensive treatment and RAS inhibition (Po0.0001). Moreover, after adjustment for the common risk factors left ventricular hypertrophy and previous myocardial infarction/stroke, these phenomena were preserved. Thus, the DD genotype of ACE may be a genetic risk factor for cerebro-cardiovascular disease, especially cardiovascular events, in hypertensive patients in Japan.

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Section: Genotypingmentioning

confidence: 99%

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

et al. 2011

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“…The detailed epidemiological findings have already been reported. [12][13][14][15][16][17] Subjects completed a standard questionnaire regarding their medical history, and smoking and drinking habits. We measured the systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, abdominal circumference, total cholesterol, triglyceride, high-density lipoprotein cholesterol, plasma glucose and immunoreactive insulin (IRI).…”

Section: Study Subjectsmentioning

confidence: 99%

Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese

et al. 2010

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It was reported that gene polymorphisms in the fat-mass and obesity-associated gene (FTO) were associated with obesity and diabetes in several genome-wide association studies. A recent report indicated that FTO-knockout mice exhibited phenotypes of skinny body shape and normal metabolic profiles. Thus, FTO could be important in metabolic disorders. The aim of this study was to clarify the role of single nucleotide polymorphisms (SNPs) in FTO in metabolic disorders such as hypertension, obesity, diabetes, dyslipidemia, insulin resistance and metabolic syndrome in the Japanese general population using data from a cohort study in Hokkaido, namely the Tanno-Sobetsu study. Written informed consent for the genetic analysis was obtained from each subject participating in the study. A total of 1514 subjects were genotyped by TaqMan PCR methods for three SNPs, rs9939609, rs1121980 and rs1558902, in FTO. Association analyses between the SNPs and metabolic parameters were performed. Although two SNPs, rs9939609 and rs1558902, were not significantly associated with hypertension, obesity, metabolic syndrome or any metabolic parameters, additive and recessive models of rs1121980 were strongly associated with plasma immunoreactive insulin (IRI) level and homeostasis model assessment insulin resistance (HOMA-IR), even after adjusting for confounding factors such as age, gender and body mass index. A haplotype of three SNPs was also significantly associated with IRI and HOMA-IR. One SNP, rs1121980, and a haplotype of three SNPs in FTO that contains this SNP, might be important in the progression of insulin resistance in Japanese subjects.

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“…The study started in 1977 with a cohort base in the northern part of Japan, Hokkaido, and the detailed epidemiological findings have been reported previously. 22 BP was measured twice in each participant while seated, after 5 minutes of rest. Hypertension was defined as systolic BP Ն140 mm Hg, diastolic BP Ն90 mm Hg, or the current use of antihypertensive agents.…”

Section: Population Study: the Tanno-sobetsu Studymentioning

confidence: 99%

A Polymorphism Regulates CYP4A11 Transcriptional Activity and Is Associated With Hypertension in a Japanese Population

et al. 2008

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Abstract-CYP4A11 oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite with renovascular and tubular function in humans. A previous study demonstrated a significant association between the CYP4A11 gene polymorphism and hypertension; however, the precise mechanism of the association has not been clarified. To assess the involvement of CYP4A11 in the pathogenesis of hypertension, we sought to identify a functional polymorphism of CYP4A11 and examined its impact on predisposition to hypertension in the Tanno-Sobetsu Study. The Ϫ845A/G polymorphism was identified in the promoter region of CYP4A11 by direct sequencing. Luciferase expression driven by the promoter of CYP4A11 containing the wild-type Ϫ845GG genotype was 30% lower than expression with the variant Ϫ845AA genotype. Gel mobility shift assays with nuclear protein extracts showed specific binding to probes containing the variant Ϫ845GG. To assess the effect of CYP4A11 polymorphisms on hypertension, we also carried out a case-control study using 4 single nucleotide polymorphisms (Ϫ845A/G, Ϫ366C/T, 7119C/T, and 8590T/C) in the Tanno-Sobetsu Study. The odds ratio for hypertension in participants with the AGϩGG genotype of Ϫ845A/G was 1.42 (Pϭ0.008), and the odds ratio for hypertension of the TT genotype of 7119C/T was 1.37 (Pϭ0.037) after adjusting for confounding factors. The haplotype-based case-control analysis using 4 single nucleotide polymorphisms revealed a significant haplotype (G-C-T-T) that was significantly associated with hypertension, with an odds ratio of 1.44 (Pϭ0.006) after adjusting for confounding factors. We have identified a functional variant (Ϫ845A/G) of CYP4A11 that is significantly associated with hypertension and that appears to be a novel candidate for a predisposing factor for hypertension. 20-HETE is normally produced in renal and cerebral arterioles, 5,6 the glomerulus, and the renal tubules 7,8 and has been implicated in the regulation of contractile state, ion flux, and mitogenesis. 20-HETE is generated from arachidonic acid by CYP4A, also known as omega/omega-1 hydroxylase. 9,10 It has been reported that administration of antisense oligonucleotides to CYP4A1 reduces BP in spontaneously hypertensive rats, 11 and the expression of CYP4A is involved in early changes in eicosanoid formation and renal function in the young spontaneously hypertensive rats. 12 The Cyp4a14 gene-disrupted mice showed increases in plasma androgens, kidney Cyp4a12 expression, and the formation of prohypertensive 20-HETE, which resulted in hypertension. 13 A recent report demonstrated that CYP4A11, originally isolated from human kidney and liver cDNA libraries, 14,15 is the human homologue of mouse CYP4a14, expressed in human renal tubule and not in afferent arterioles. The report also described CYP4A11 regulation of 20-HETE. 16 Despite the potential involvement of CYP4A11 in regulating BP through 20-HETE, the exact function of the CYP4A11 gene is still unknown.

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Effects of Angiotensin II Type 1 Receptor Gene Polymorphisms on Insulin Resistance in a Japanese General Population: The Tanno-Sobetsu Study

Cited by 25 publications

References 40 publications

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients

Association of gene polymorphism of the fat-mass and obesity-associated gene with insulin resistance in Japanese

A Polymorphism Regulates CYP4A11 Transcriptional Activity and Is Associated With Hypertension in a Japanese Population

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