Effect of 9p21.3 (lncRNA and CDKN2A/2B) variant on lipid profile

Abstract

BackgroundSeveral 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are reported to be associated with coronary artery disease (CAD) susceptibility but independent of dyslipidemia. This study investigated whether these 9p21.3 variants influenced lipid profiles.Methods and resultsBy searching the PubMed and Cochrane databases, 101,099 individuals were included in the analysis. The consistent finding for the rs1333049 C allele on lipid profiles increased the triglyceride (TG) levels. Moreover, the rs4977574 G allele and the rs10757274 G allele, respectively, increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. However, the rs10811661 C allele largely reduced LDL-C levels. Subgroup analyses indicated that the effects of the rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele on lipid profiles were stronger in Whites compared with Asians. In contrast, the effect of the rs10811661 C allele on lipid profiles was stronger in Asians compared with Whites.ConclusionThe rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele of lncRNA, and the rs10811661 G allele of CDKN2A/2B had a significant influence on lipid levels, which may help the understanding of the underlying mechanisms between 9p21.3 variants and CAD.

Influence of Chromosome 9p21.3 rs1333049 Variant on Telomere Length and Their Interactive Impact on the Prognosis of Coronary Artery Disease

“…Of note, the locus seems not to be linked to any conventional CAD risk factors, even if several variants have been reported to influence the lipid profile [ 23 ]. However, it may exert its effect through a completely novel biological mechanism related to vascular integrity and atherosclerosis development [ 24 ].…”

Deletion of the Murine Ortholog of the Human 9p21.3 Locus Leads to Insulin Resistance and Obesity in Hypercholesterolemic Mice

“…Initially, the CAD risk associated with 9p21.3 genetic variants and ANRIL expression was reported being independent of traditional CAD risk factors like sex, smoking, obesity, hypertension, or diabetes [ 15 , 16 , 17 ]. However, recent studies have reported 9p21.3 risk variants having an effect on plasma lipid profile and lipid uptake in vascular cells [ 18 , 19 ]. The VITA cohort study also revealed that elevated circulating levels of ANRIL may predict later onset of T2D [ 20 ].…”