Genome‐wide association study validation identifies novel loci for atherosclerotic cardiovascular disease

Abstract

). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (P meta-analysis < 5.43 · 10 )4). In addition, we found that a missense variant of KLF14, rs11140 0400 (Ser58Pro), was associated with MI. Conclusion: Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes.

Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production

“…In an attempt to identify genes that may play a critical role in regulation of lipid metabolism using real-time polymerase chain reaction (PCR) analysis, we first examined the expression profiles of 43 candidate genes that are associated with the HDL-C trait and CHD, as indicated by previous GWAS (17)(18)(19)21), in the liver from 2 dyslipidemia mouse models. We found that Klf14 mRNA expression was significantly decreased, by approximately 70%, in the liver of C57BL/6 mice in response to a high-fat diet (HFD) (Supplemental Figure 1, A and B; supplemental material available online with this article; doi:10.1172/JCI79048DS1).…”

“…Large-scale GWAS have identified that a genetic variant on chromosome 7 is strongly associated with both HDL trait and CHD (17)(18)(19)(20)(21). This variant lies in a noncoding region in the vicinity of KLF14 and TSGA13, which encode Krüppel-like factor 14 and testis-specific gene A13, respectively.…”

“…The 18 KLFs described in mammals possess highly conserved cysteine and histamine zinc fingers, critical for recognition and binding to CACCC or CGCCC DNA motifs (22). KLF14, a maternally expressed imprinted gene without introns, is robustly associated with HDL-C levels, CHD, type 2 diabetes, obesity, and cancer (17,18,20,21,(23)(24)(25)(26)(27)(28). In fact, KLF14 has been recently proposed as a master trans-regulator of multiple genes that are associated with metabolic phenotypes in adipose tissue (26), T regulatory cell differentiation (29), and lipid-mediated signaling through a distinct epigenetic mechanism (20), though its role in lipid metabolism and CVD remains to be determined.…”

The Association between the KLF14 rs4731702 SNP and the Lipid Profile in Type 2 Diabetes Mellitus Patients: A Study in San Luis City, San Luis, Argentina

“…Moreover, the minor T allele frequency in myocardial infarction and ischemic stroke groups in these populations was lower than that in their corresponding control groups. The frequency of T allele was 31.5%, 29.1%, and 30.2% in the three control groups, respectively [5].…”

Interleukin 10 rs1800872 T>G Polymorphism was Associated with an Increased Risk of Esophageal Cancer in a Chinese Population

“…Sample DNA (10 ng) were amplified by PCR according to the manufacturer's recommendations. The SNP genotyping work was performed using a custom-bydesign 48-Plex SNPscan TM Kit (Genesky Biotechnologies Inc., Shanghai, China) as previously described (Chen et al, 2012). This kit was developed according to patented SNP genotyping technology by Genesky Biotechnologies Inc., which was based on double ligation and multiplex fluorescence PCR.…”