Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension.
BACKGROUND
As 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).


METHODS
To 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.


RESULTS
Eight 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.


CONCLUSIONS
Our 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.
Kardia
Sharon L R
SL
Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA. skardia@umich.edu
Sun
Yan V
YV
Hamon
Sara C
SC
Barkley
Ruth Ann
RA
Boerwinkle
Eric
E
Turner
Stephen T
ST
D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D015810:Linkage Disequilibrium; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012044:Regression Analysis; D000099291:Adducins
D000959:Antihypertensive Agents; D003598:Cytoskeletal Proteins; D005819:Genetic Markers; C501062:ADD2 protein, human; D000099291:Adducins