The T Allele of rs8075977 in the 5’-Flanking Region of the PEDF Gene Is Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men

The T Allele of rs8075977 in the 5'-Flanking Region of the PEDF Gene Is Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men

SHOU-YUAN MA,¹ YUAN-YUAN GUO,² SHU-XIA WANG,³ JIN-XIN SHI,² JIE LIU,⁴ JIAN-FENG LIU¹ and PING ZHU¹

¹Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China
²Department of Cardiovascular Medicine, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, China
³Department of Cadre Clinic, Chinese PLA General Hospital, Beijing, China
⁴Department of Geriatrics, Civil Aviation General Hospital, Beijing, China

Coronary artery disease (CAD) is a multifactorial disease with a genetic component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received increasing attention as a sensitive biomarker of atherosclerosis and CAD. To explore the potential association between PEDF single nucleotide polymorphisms (SNPs) and CAD, we performed this case-control study of consecutive elderly Chinese Han male patients (n = 416) and age-matched male controls (n = 528) without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD patients (age ge; 60 years) are not biologically related. A tag approach was used to examine 100% of common variations in the PEDF gene (r² ≥ 0.8, minor allele frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB which describes the common patterns of human DNA sequence variation and Tagger program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs (rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634) were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'-flanking region, showed the significant effect on the susceptibility to CAD. The frequency of its T allele was significantly higher in the controls (52.7%) than that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005). In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF gene may be protective for CAD. Conversely, the C allele at this variation site is associated with CAD in elderly Chinese Han men.

keywords —— coronary artery disease; ligase detection reaction; pigment epithelium-derived factor; risk factor; single nucleotide polymorphisms

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Tohoku J. Exp. Med., 2017, 241, 297-308

Correspondence: Ping Zhu, Department of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.

e-mail: zhuping301@139.com