Dr. Ana I. Vázquez, assistant professor in the department of biostatistics at the University of Alabama at Birmingham, recently investigated whether there is a genotype-by-treatment interaction in patients experiencing stroke and being treated with one of the following three antihypertensive drugs: chlorthalidone, amlodipine, or lisinopril. Co-investigators include Dr. Izel F. Sørensen and Dr. Peter Sørensen, former visiting scholars in UAB’s department of biostatistics, section on statistical genetics, as well as Dr. Donna K. Arnett, professor and chair, and Dr. M. Ryan Irvin, assistant professor, in UAB’s department of epidemiology.
A population of 436 African Americans and 539 Whites who had experienced stroke in the GenHAT study — which examined “whether the association between selected hypertensive genes and combined fatal coronary heart disease and nonfatal myocardial infarction in high-risk hypertensives is modified by the type of antihypertensive treatment, leading to differential risks of coronary heart disease” — were genotyped for 768 single nucleotide polymorphisms (SNPs) in 280 candidate genes. To detect a genotype-by-treatment interaction, the researchers used the Pearson’s χ-test to assess whether the genotype frequencies differed at the single SNP level for the three drug treatment groups. From these single SNP analyses, they derived a summary statistic for the degree of association at the gene and gene complex levels, which was achieved by grouping SNPs using information on gene locations and defining gene complexes on the basis of protein-protein interactions. To assess the statistical significance of the observed test statistic, the team derived an empirical P-value by simulating data under the null hypothesis.
Results indicated that, in patients who have experienced stroke, there is a significant genetic difference between hypertension drug treatment groups. In African Americans, SNP rs12143842 showed a significant association with drug treatment. At the gene level, HNRNPA1P4 and NOS1AP in African Americans and PRICKLE1 and NINJ2 in non-Hispanic Whites were significantly associated with drug treatment, whereas none of the gene complexes tested showed significance.
On the basis of the genetic differences between drug treatment groups, Dr. Vázquez and her colleagues conclude that there may be an interaction between certain genotypes and antihypertensive treatment in stroke patients, indicating that further studies need to be conducted to replicate results.
“Pharmacogenetic Effects of ‘Candidate Gene Complexes’ on Stroke in the GenHAT Study” was published in November in the journal Pharmacogenetics and Genomics.