RYR3 gene polymorphisms and cardiovascular disease outcomes in the context of antihypertensive treatment.

Nearly one-third of adults in the United States 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 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 (HF) 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 HF, the strongest of which was for rs877087, with the smallest P-value=0.0005 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 3058 CHD cases and 1940 HF cases show that a hypertensive patient's genetic profile may help predict which medication(s) might better lower CVD risk.

Evaluating linkage disequilibrium and recombination provides a haplotype-tagging SNP panel of the major histocompatibility complex in African Americans.

The major histocompatibility complex (MHC) (Chromosome 6p21.3) is a dynamic, immune gene-rich region that is associated with multiple diseases. Haplotype-tagging single-nucleotide polymorphism (htSNP) panels for the MHC can aid association studies but have only been reported for African, Asian and Caucasian populations to date. We genotyped 2154 SNPs spanning a 3.8-Mb region of the classical MHC in 94 healthy African Americans using Illumina BeadArray technology. We describe the haplotype structure of the MHC in African Americans, calculate the recombination rate (0.35 cM Mb(-1)) across the region, identify recombination hot spots and develop a panel of htSNPs for future genetic association studies in this population. We conclude that while patterns of LD and recombination are similar within the MHC to that reported in other populations, differences in minor allele frequency at specific markers necessitates an htSNP panel unique to African Americans, which we provide here for use in future genetic association studies.

Effects of endurance training on body-consciousness in women.

The Body Consciousness Questionnaire by Miller, Murphy, and Buss in 1981 was employed to assess the effects of intensive endurance training on changes in self-perception in 13 women volunteers aged 20 to 30 yr. The participants engaged in an intensive progressive running program for 6 to 8 wk. Additional moderate exercise (softball or volleyball) was engaged in for 3 1/2 hr. per day. Before and after the training subjects completed the questionnaire on self-perceived attributes of internal body consciousness, public body consciousness, and body competence. Aerobic fitness, measured pre- and posttraining, significantly increased while body fat and weight significantly decreased. In consonance with these physiological changes, rated self-perception of internal body consciousness and body competence increased significantly while public body consciousness remained unchanged. Self-report of internal body consciousness tended to increase in proportion to changes in fitness (r = 0.53). These results suggest that endurance and moderate exercise training contribute to increased self-perception specifically with regard to perceived internal and body competence.