Genome-Wide Linkage Analyses of Systolic Blood Pressure Using Highly Discordant Siblings

Krushkal, Julia; Ferrell, Robert E.; Mockrin, Stephen; Turner, Stephen T.; Sing, Charles F.; Boerwinkle, Eric

doi:10.1161/01.cir.99.11.1407

Cited by 198 publications

(137 citation statements)

References 13 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Multiple linkage analyses have provided statistical evidence that one or more genes on chromosome 2 between 40 and 140 cM from the tip of the p-arm influence blood pressure and hypertension status. [2][3][4][5][6][7][8] Broad linkage peaks shifted across the chromosome and the fact that every study sample does not reveal a noticeable peak in the same region are consistent with the expectation that multiple genes, each with a small effect, influence blood pressure and contribute to hypertension. The present study reports the results of a study to follow-up evidence of significant linkage on chromosome 2 to identify genes that may influence hypertension status and/or blood pressure level.…”

supporting

confidence: 77%

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

et al. 2004

Self Cite

View full text Add to dashboard Cite

Abstract-Chromosome 2 has been consistently identified as a genomic region with genetic linkage evidence suggesting that one or more loci contributes to blood pressure and hypertension status. As with all complex disease traits, following-up linkage evidence to identify the underlying susceptibility gene(s) is an arduous yet biologically and clinically important task. Using combined positional candidate gene methods, the Family Blood Pressure Program (FBPP) has concentrated efforts in narrowing a large region of chromosome 2, demonstrating evidence for linkage in several populations, and identifying underlying candidate hypertension susceptibility gene(s). Initial informatics efforts identified the boundaries of the region and the known genes within it. A total of 82 polymorphic sites in 8 genes were genotyped in a large hypothesis-generating sample consisting of 1640 African Americans, 1339 whites, and 1616 Mexican Americans. After resampling-based false discovery adjustment, SLC4A5, a sodium bicarbonate transporter, was identified as a primary candidate gene for hypertension. Polymorphisms in SLC4A5 were subsequently genotyped and analyzed for validation in two other subcomponents of the FBPP, each contributing African Americans (Nϭ461; Nϭ778) and whites (Nϭ550; Nϭ967). Again, single nucleotide polymorphisms within this gene were significantly associated with blood pressure levels and hypertension status. Although not identifying a single causal gene variant that is significantly associated with blood pressure levels and hypertension status across all samples, the results further implicate SLC4A5 as a candidate hypertension susceptibility gene. Moreover, the present study validates previous evidence for one or more genes on chromosome 2 that influence hypertension-related phenotypes in the population-at-large.

show abstract

supporting

confidence: 77%

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, Angius et al reported strong evidence that a 0.54-cM region of chromosome 2 (2p 26.5-27.1) harbors a locus-affecting risk of hypertension in an isolated Sardinian population (45). In addition, a number of regions of chromosome 2 (57-59, 86, 103, and 96-115 cM) have been found likely to harbor blood-pressure-modifying loci (45)(46)(47)(48). More importantly, our group recently reported some hypertension-susceptibility genes at 2p24-p25 and a positive relationship between hypertension and SNPs of the Na + /Ca 2+ exchanger 1 gene, which is located at 2p22-p23, in a general Japanese population (49,50).…”

Section: Discussionmentioning

confidence: 99%

Assiciations of Hypertension and Its Complications with Variations in the Xanthine Dehydrogenase Gene

Yang¹,

Kamide²,

Kokubo³

et al. 2008

Hypertens Res

View full text Add to dashboard Cite

show abstract

“…26 Some of the reports have shown that 2p, on which the FSHR gene is located, is associated with the candidate loci for EH. [27][28][29][30][31][32] However, these regions are broad, and there has been no definite susceptibility gene identified in this region. Although like our study in which the strategy for identification of susceptibility genes of EH was different between the genome-wide scans and case-control studies, the final goal for identifying the causal mutation for EH was the same.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

View full text Add to dashboard Cite

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...

show abstract

Genome-Wide Linkage Analyses of Systolic Blood Pressure Using Highly Discordant Siblings

Cited by 198 publications

References 13 publications

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

Positional Identification of Hypertension Susceptibility Genes on Chromosome 2

Assiciations of Hypertension and Its Complications with Variations in the Xanthine Dehydrogenase Gene

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

Contact Info

Product

Resources

About