Interactions between the adducin 2gene and antihypertensive drug therapies in determining blood pressure in people with hypertensionReport as inadecuate




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BMC Medical Genetics

, 8:61

First Online: 13 September 2007Received: 28 February 2007Accepted: 13 September 2007

Abstract

BackgroundAs part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy GENOA recruited 575 sibships n = 1583 individuals from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms SNPs typed in 7 positional candidate genes, including adducin 2 ADD2.

MethodTo investigate whether blood pressure BP levels in these hypertensives n = 1133 were influenced by gene-by-drug interactions, we used cross-validation statistical methods i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup. These methods greatly reduced the chance of false positive findings.

ResultsEight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives p-value < 0.05. Moreover, we also identified SNPs associated with gene-by-drug interactions on systolic BP in drug-treated hypertensives. The TT genotype at SNP rs1541582 was associated with an average systolic BP of 133 mmHg in the beta-blocker subgroup and 148 mmHg in the diuretic subgroup after adjusting for overall mean differences among drug classes.

ConclusionOur findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-8-61 contains supplementary material, which is available to authorized users.

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Author: Sharon LR Kardia - Yan V Sun - Sara C Hamon - Ruth Ann Barkley - Eric Boerwinkle - Stephen T Turner

Source: https://link.springer.com/



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