Abstract
BackgroundInsulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM.MethodsWe selected and genotyped 5 haplotype-tagging single nucleotide polymorphisms (SNPs) at PCSK1 gene (across 39873bp locus) in a case-control study of Chinese Han population involving 425 diabetic patients (62.1% male, mean age 63.2 years) with CAD as positive cases and 258 diabetic patients (44.2% male, mean age 62.0 years) without CAD as controls.ResultsThe allele frequencies at rs3811951 were significantly different between cases and controls (30.7% vs. 37.2%), with the allele G associated with decreased risk for CAD (OR = 0.75, 95% CI = 0.59–0.94, p = 0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR = 0.50, 95%CI = 0.31–0.82, p = 0.005), even after adjusted for gender, age, BMI and smoking (OR = 0.43, 95%CI = 0.24–0.77, p = 0.004). The carriers of the minor allele A at rs156019 had a higher risk (OR = 1.66, 95%CI = 1.10–2.50, p = 0.016 after adjustment) in dominant inheritance mode. The SNP rs6234 was also significantly associated with CAD risk in women, with the carriers of the minor allele G at rs6234 associated with a reduced CAD risk in recessive inheritance mode (OR = 0.42, 95% CI = 0.18–0.95, p = 0.036 after adjustment).ConclusionsOur results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM.
Highlights
Coronary artery disease (CAD), characterized by the formation of atheromatous plaques, is one of the major complications and accounts for the majority of deaths of type 2 diabetes (T2DM)
In order to find out the common genetic pathogenesis of coronary artery disease (CAD) and T2DM and reduce the mortality of the two killers, it is clinically critical to screen out the genetic variants at a high risk of CAD in T2DM and further take individualized and positive measures in primary prevention as early as possible
While relative or absolute lack of insulin is the characteristics of T2DM, insulin is involved in the development of atherosclerosis
Summary
Coronary artery disease (CAD), characterized by the formation of atheromatous plaques, is one of the major complications and accounts for the majority of deaths of type 2 diabetes (T2DM). Glucagon like peptide 1 (GLP-1), as another hormone that is developed into an anti-diabetic drug, can inhibit the formation of atheromatous plaques by its regulation of endothelium, vascular smooth muscle cells, monocytes and macrophages [5]. Insulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM
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