Carotid intima-media thickness (cIMT) is a subclinical measure of atherosclerosis with mounting evidence that higher cIMT confers an increased risk of cardiovascular disease. The ryanodine receptor three gene (RYR3) has previously been linked to increased cIMT; however, the causal variants have not yet been localized. Therefore, Dr. Degui Zhi, assistant professor in the department of biostatistics, section on statistical genetics, and senior author Dr. Sadeep Shrestha, associate professor in the department of epidemiology, at the University of Alabama at Birmingham, sequenced 339 480 bp encompassing 104 exons and two kb flanking region of the RYR3 gene in 96 HIV-positive White men from the extremes of the distribution of common cIMT from the Fat Redistribution and Metabolic Changes in HIV infection study (FRAM). Co-investigators include UAB department colleagues Dr. M. Ryan Irvin, assistant professor, Dr. Rodney T. Perry, research assistant professor, Dr. Shawn E. Levy, adjunct associate professor, Ms. Aditi D. Shendre, graduate assistant, and Dr. Donna K. Arnett, professor and chair; as well collaborators from the University of California, San Francisco, Drs. Carl Grunfeld and Rebecca Scherzer.
The team identified 2,710 confirmed variants (2,414 single-nucleotide polymorphisms, or SNPs) and 296 insertion/deletions (indels), with a mean count of 736 SNPs (ranging from 528 to 1,032) and 170 indels (ranging from 128 to 214) distributed in each individual. There were 39 variants in the exons and 15 of these were non-synonymous, of which only 4 were common variants and the remaining 11 were rare variants, with one a novel SNP.
Drs. Zhi and Shrestha and their fellow researchers confirmed that the common variant rs2229116 was significantly associated with cIMT in this design and observed seven other significantly associated SNPs. These variants including the private non-synonymous SNPs need to be followed up in a larger sample size and also tested with clinical atherosclerotic outcomes.
“Deep Sequencing of RYR3 Gene Identifies Rare and Common Variants Associated with Increased Carotid Intima-media Thickness (cIMT) in HIV-infected Individuals” was published in December 2014 in the Journal of Human Genetics.