An association study in essential hypertension using functional polymorphisms in lymphotoxin-? gene

Nakayama, Tomohiro; Soma, Masayoshi; Sato, Naoyuki; Haketa, Akira; Kosuge, Kotoko; Aoi, Noriko; Sato, Mitsugu; Izumi, Yasukatsu; Matsumoto, Koichí; Kanmatsuse, Katsuo

doi:10.1016/j.amjhyper.2004.07.010

Cited by 18 publications

(17 citation statements)

References 27 publications

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“…18 Informed consent was obtained from each subject in accordance with a protocol approved by the Human Studies Committee of Nihon University. 19 Genotyping. There are 225 SNPs for the human CYP4F2 gene listed in the National Center for Biotechnology Information SNP database Build 126 (http://www.ncbi.nlm.nih.gov/SNP).…”

Section: Subjectsmentioning

confidence: 99%

A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

Nakayama

Sato

et al. 2008

American Journal of Hypertension

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Section: Subjectsmentioning

confidence: 99%

A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

Nakayama

Sato

et al. 2008

American Journal of Hypertension

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“…Informed consent was obtained from each individual as per a protocol approved by the Human Studies Committee of Nihon University. 15 …”

Section: Methods First Case-control Studymentioning

confidence: 99%

Mutation of the Follicle-Stimulating Hormone Receptor Gene 5′-Untranslated Region Associated With Female Hypertension

et al. 2006

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Abstract-Inactivating mutations in the follicle-stimulating hormone receptor (FSHR) gene have been reported to cause hereditary hypergonadotropic ovarian failure. It has been found recently that the FSHR knockout mouse exhibits hypertension. The aim of the present study was to investigate the association between polymorphisms in the human FSHR gene and essential hypertension (EH) by using single nucleotide polymorphisms (SNPs). We selected 5 SNPs in the gene (rs1394205, rs2055571, rs11692782, rs1007541, and rs2268361) and performed 2 genetic case-control studies in different populations. A confirmative case-control study was performed using 1035 EH patients and 1058 age-matched controls. Transcriptional activities were measured with a luciferase assay system. The first case-control study found that the A allele of rs1394205 was significantly higher in EH females (Pϭ0.010). In addition, in the confirmative case-control study, there was a significant difference for this SNP between female normotensive subjects (44.5%) and EH patients (50.7%) (Pϭ0.043). Multiple logistic regression analysis in female subjects also revealed a significant association of subjects with the A allele of rs1394205 with EH (Pϭ0.033), with the odds ratio calculated as 1.68 (95% CI: 1.04 to 2.73). Transcriptional activity of the A allele was 56Ϯ8% (meanϮSD) of that observed for the G-type allele (Pϭ0.001). Serum estradiol levels were significantly lower in patients with the A/A genotype than in patients without the A/A genotype (Pϭ0.004). The SNP in the 5Ј-untranslated region of the FSHR gene affects levels of transcriptional activity and is a susceptibility mutation of EH in women. Key Words: hypertension, essential Ⅲ hormones Ⅲ case-control studies I t is likely that essential hypertension (EH) is a polygenic disorder that results from the inheritance of a number of susceptibility genes. The causal genes identified may contribute from 30% to 50% of the variations in blood pressure seen among individuals. 1 These genetic determinants interact with environmental factors, such as dietary salt, to produce the final disease phenotype. Despite significant recent progress in genomic and statistical tools, the genetic dissection of human EH remains a major challenge. 2 The effects of follicle-stimulating hormone (FSH) are mediated by its interaction with specific receptors and the activation of G s , the stimulatory guanine nucleotide binding protein, which stimulates the enzyme adenylyl cyclase. 3 The FSH receptor (FSHR) belongs to the superfamily of G proteincoupled receptors that are characterized by the common structural feature of 7 transmembrane domains. They differ structurally from other G protein-coupled receptors in that they contain a large extracellular domain in the amino-terminal part of the receptor protein, which is required for interaction with complex glycoprotein hormones. 4 -6 The human FSHR gene is localized to 2p21 to p16 and is composed of 10 exons. 7 The 5Ј-flanking region of the gene has neither a TATA nor a CCAAT box and...

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“…This polymorphism was further linked to the extent of coronary atherosclerosis [87]. None of the three polymorphisms of the LTA gene was found to be associated with essential hypertension [88]. It seems evident that further studies are needed to test the association of LTA variants with CVD.…”

Section: Lymphotoxin-alphamentioning

confidence: 97%

Genetic variants predisposing to cardiovascular disease

Visvikis‐Siest

Marteau

2006

Current Opinion in Lipidology

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During the last year, tremendous effort has been made in elucidating new genes associated with cardiovascular disease predisposition. For the most part, however, major breakthroughs have not been made, primarily due to the poor replication of results among studies, as a consequence of poor experimental design. Nevertheless, we have increased our understanding of the complexity of cardiovascular disease and the relevance of gene-environment interactions as the ultimate drivers of the individual predisposition to the disease. It is essential, therefore, that present and future genetic studies in this area take into consideration the inclusion of high-quality environmental data in the analytical process to test the clinical usefulness of a genetic marker as a risk predictor.

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An association study in essential hypertension using functional polymorphisms in lymphotoxin-? gene

Abstract: Polymorphisms of the LTA gene were not associated with EH. This finding suggests differences in genetic backgrounds between EH and MI.

Cited by 18 publications

References 27 publications

A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

Mutation of the Follicle-Stimulating Hormone Receptor Gene 5′-Untranslated Region Associated With Female Hypertension

Genetic variants predisposing to cardiovascular disease

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