Genetic variants in PCSK1 gene are associated with the risk of coronary artery disease in type 2 diabetes in a Chinese Han population: a case control study.
BACKGROUND
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.


METHODS
We 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.


RESULTS
The 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).


CONCLUSIONS
Our results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM.
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Xiaowei
X
Wei
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Xiaowei
X
Ma
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Ran
R
Lu
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Ge
G
Bai
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Jianwei
J
Zhang
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Ruifen
R
Deng
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Nan
N
Gu
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Nan
N
Feng
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Xiaohui
X
Guo
D000368:Aged; D016022:Case-Control Studies; D002681:China; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D045664:Proprotein Convertase 1 / Q000235:genetics*
C587576:PCSK1 protein, human; D045664:Proprotein Convertase 1