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1.  RYR3 gene polymorphisms and cardiovascular disease outcomes in the context of antihypertensive treatment 
The pharmacogenomics journal  2012;13(4):330-334.
Nearly one-third of adults in the U.S. have hypertension, which is associated with increased cardiovascular disease (CVD) morbidity and mortality. The goal of antihypertensive pharmacogenetic research is to enhance understanding of drug response based on the interaction of individual genetic architecture and antihypertensive therapy to improve blood pressure control and ultimately prevent CVD outcomes. In the context of the Genetics of Hypertension Associated Treatment (GenHAT) study and using a case-only design, we examined whether single nucleotide polymorphisms in RYR3 interact with four classes of antihypertensive drugs, particularly the calcium channel blocker amlodipine versus other classes, to modify the risk of coronary heart disease (CHD; fatal CHD and non-fatal myocardial infarction combined) and heart failure in high-risk hypertensive individuals. RYR3 mediates the mobilization of stored Ca+2 in cardiac and skeletal muscle to initiate muscle contraction. There was suggestive evidence of pharmacogenetic effects on heart failure, the strongest of which was for rs877087, with the smallest p-value =.0005 for the codominant model when comparing amlodipine versus all other treatments. There were no pharmacogenetic effects observed for CHD. The findings reported here for the case-only analysis of the antihypertensive pharmacogenetic effect of RYR3 among 3,058 CHD cases and 1,940 heart failure cases show that a hypertensive patient’s genetic profile may help predict which medication(s) might better lower cardiovascular disease risk.
doi:10.1038/tpj.2012.22
PMCID: PMC3435442  PMID: 22664477
RYR3 gene; calcium channel blocker; hypertension; coronary heart disease; heart failure; genetic interaction
2.  A Genome-wide Association Study of Carotid Atherosclerosis in HIV-infected Men 
AIDS (London, England)  2010;24(4):583-592.
Background
The role of host genetics in the development of subclinical atherosclerosis in the context of HIV infected persons who are being treated with highly active antiretroviral therapy (HAART) is not well understood.
Methods
The present genome-wide association study (GWAS) is based on 177 HIV-positive Caucasian males receiving HAART who participated in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) Study. Common and internal carotid intima-media thicknesses (cIMT) measured by B-mode ultrasound were used as a subclinical measure of atherosclerosis. Single nucleotide polymorphisms (SNPs) were assayed using the Illumina HumanCNV370-quad beadchip. Copy Number Variants (CNV) were inferred using a hidden Markov Model (PennCNV). Regression analyses were used to assess the association of common and internal cIMT with individual SNPs and CNVs, adjusting for age, duration of antiretroviral treatment, and principal components to account for potential population stratification.
Results
Two SNPs in tight linkage disequilibrium, rs2229116 (a missense, nonsynonymous polymorphism (IIe to Val)) and rs7177922, located in the Ryanodine receptor (RYR3) gene on chromosome 15 were significantly associated with common cIMT (p-value<1.61×10−7). The RYR gene family has been known to play a role in the etiology of cardiovascular disease and has been shown to be regulated by HIV TAT protein.
Conclusions
These results suggest that in the context of HIV infection and HAART, a functional SNP in a biologically plausible candidate gene, RYR3, is associated with increased common carotid IMT, which is a surrogate for atherosclerosis.
doi:10.1097/QAD.0b013e3283353c9e
PMCID: PMC3072760  PMID: 20009918
HIV; HAART; atherosclerosis; GWAS; intima-media thickness

Results 1-2 (2)