“Desert” gene (Chr9p21) variants as novel markers for coronary artery disease

Abstract

Objective:Previous reports have denoted to the possible link of Chr9p21 locus to the incidence of coronary artery disease (CAD). The entire core of chr9p21 is covered by “ANRIL” (Antisense noncoding RNA in INK4 Locus) and lies in a region that is free from any coding proteins; therefore, it is called the desert gene. The major objectives of this study were to examine the association of rs10757278 and rs2383206 SNPs on Chr9p21 with the incidence of CAD in the presence and absence of type 2 diabetes (T2D) in Egyptians and to correlate these genetic variants with several disease biomarkers (TC, CRP, and HbA1c).Methods:The study subjects consisted of 150 subjects; 50 healthy controls and 100 patients that were divided into two groups; CAD patients and CAD T2D patients. The genotyping of SNPs was performed using qPCR.Results:Genotype distribution for both SNPs were found to be significantly different (p=0.0009 for rs10757278 and p=0.001 for rs2383206) between patients and controls. The allele frequency was also different for rs10757278.Conclusion:The current study showed that rs10757278/rs2383206-G allele increases the risk for CAD in Egyptians. Moreover, AA variant appeared as a protective genotype. However, SNPs did not noticeably contribute in the elevation of TC, hs-CRP, and HbA1c in non-diabetic and diabetic CAD patients.

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease

“…Nevertheless, downregulation of ANRIL in CAD patients was also documented in other studies [49][50][51]. This discrepancy could be attributed to different Chr9p21 locus genotypes as the Chr9p21 rs10757278/rs2383206-G risk allele associated with increased ANRIL expression is prevalent in Egyptian CAD patients [52,53]. In fact, and to our knowledge, this study addressed for the first time the upregulated expression level of CDK4 and E-cadherin in CAD patients.…”

ANRIL and atherosclerosis

“…Samaneh et al demonstrated in a cohort study, which enrolled 420 patients with CHD from the population of the Tehran lipid and glucose study (TLGS) and matched 407 healthy controls with age and sex, that the presence of risk alleles of an ANRIL SNP (rs7865618) was associated with CHD ( P = .03; OR: 1.73; CI 95%: 1.04‐2.88) . Heba et al conducted a case‐control study consisting of 50 healthy individuals and 100 patients and found that the rs10757278 (OR: 1.92, P = .0002) and rs2383206 (OR: 1.729, P = .0004) SNPs in ANRIL ( P < .001) increased the risk for CAD . In a case‐control study including 33 T2DM patients with CHD and 31 T2DM patients alone, Esmaeil et al found that the expression of ANRIL was associated with CHD in diabetic patients, and ANRIL was upregulated (2.34‐fold, P = .012) in T2DM with CHD.…”