Dissecting complex traits: recent advances in hypertension genomics

O’Shaughnessy, Kevin M.

doi:10.1186/gm43

Cited by 14 publications

(16 citation statements)

References 38 publications

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“…This SNP showed a difference in MAF of about 4.4% between hypertensive and normotensive subjects, and a difference in diastolic blood pressure of about 1.3 mmHg between subjects with CC and GG genotypes. Such small effect size is consistent with the findings from recent genome-wide association studies (30,31). Nevertheless, our findings will need to be confirmed by an independent larger prospective cohort with a better power to detect associations with smaller effect size.…”

Section: Discussionsupporting

confidence: 80%

Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese

Ong¹,

Li²,

Tso

et al. 2010

European Journal of Endocrinology

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Objective: Low plasma adiponectin level can predict the development of hypertension after 5 years in our population. We therefore investigated whether single-nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with hypertension. Design and methods: We genotyped 14 tagging SNPs in 1616 subjects with persistent normotensive or hypertensive status during a 6.4-year follow-up period in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2). Plasma adiponectin level was measured in 1385 subjects using in-house sandwich ELISA. Results: The minor G allele of the SNP rs266729 was significantly associated with higher odds of hypertension (odds ratio (95% confidence interval)Z1.49 (1.13-1.95), PZ0.0044) after adjusting for covariates. In stepwise multiple logistic regression, this SNP (PZ0.006) was a significant independent factor of hypertension, together with age (P!0.001), body mass index (P!0.001), triglycerides (PZ0.021), and insulin resistance index (P!0.001). Among the 14 SNPs, rs266729 (bZK0.067, PZ0.0037), K10677COT (bZ0.069, PZ0.0027), rs182052 (bZK0.097, P!0.0001), and rs12495941 (bZ0.103, P!0.0001) were significantly associated with adiponectin level after adjusting for covariates. No significant sex interaction was found for the associations of SNPs with hypertension and adiponectin level. Similar results were obtained in haplotype analysis. Conclusion: In our population, genetic variants in the adiponectin gene influenced plasma adiponectin levels, and one of them was associated with hypertension. This study has provided further evidence for a role of adiponectin in the development of hypertension.

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Section: Discussionsupporting

confidence: 80%

Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese

Ong¹,

Li²,

Tso

et al. 2010

European Journal of Endocrinology

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“…The genetic component of human blood pressure variation may be attributable to many genetic variants each expressed in a relatively small percentage of the population. As the resolution of genomic mapping increases and analytic techniques improve, the relevance to the general population of the familial or mendelian forms of altered blood pressure may become greater for understanding blood pressure in the general population [46,47]. …”

Section: Discussionmentioning

confidence: 99%

Genetic Disorders of NaCl Transport in the Distal Convoluted Tubule

Miller

2010

Nephron Physiol

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The distal convoluted tubule (DCT) reabsorbs 5–10% of filtered Na, and is an important site for regulation of Na balance. Additionally, the amount and composition of the tubular fluid that leaves the DCT affects H and K secretion in more distal nephrin segments. Mutations in five genes whose products are expressed in the DCT demonstrate these points and help to define the mechanisms by which the DCT contributes to control of electrolyte balance and volume. Loss of function mutations in the apical thiazide-sensitive NaCl cotransporter and the basolateral K channel Kir4.1, and activating mutations in the Ca-sensing receptor cause a phenotypically similar salt wasting syndrome. Mutation in two recently identified kinases, WNK1 and WNK4 cause a salt-retaining syndrome through increased apical expression of NaCl cotransporter. Recent studies indicate that these genes are important not only for understanding the physiology of the distal nephron, but that they and others may also contribute to blood pressure variation in the general population.

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“…In addition to the influences of age and gender, a number of environmental factors affect BP, including poor diet, lack of exercise, increased body weight, stress, smoking and alcohol intake [15] . Aside from the identification of causal mutations for various monogenic forms of familial hypertension [16,17] , there have been continued efforts to localize susceptibility loci for BP or hypertension in the general population. Several genome-wide linkage screens have been performed to localize genes for BP or hypertension, which found evidence for suggestive or significant linkage signals on several chromosomal regions, e.g.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Linkage Screen for Systolic Blood Pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and Confirmation of a Major Susceptibility Locus on Chromosome 6q14.1

Puppala

Coletta²,

Schneider

et al. 2011

Hum Hered

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Objective: Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES). Methods: Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911–2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/ 90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values. Results: The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans.

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Dissecting complex traits: recent advances in hypertension genomics

Cited by 14 publications

References 38 publications

Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese

Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese

Genetic Disorders of NaCl Transport in the Distal Convoluted Tubule

Genome-Wide Linkage Screen for Systolic Blood Pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and Confirmation of a Major Susceptibility Locus on Chromosome 6q14.1

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