A Polymorphism inHepatocyte Nuclear Factor 1 Alpha,rs7310409, Is Associated with Left Main Coronary Artery Disease

Abstract

Coronary artery disease is the leading cause of mortality and morbidity in the world. Left main coronary artery disease (LMCAD) is a particularly severe phenotypic form of CAD and has a genetic basis. We hypothesized that some inflammation- and hyperhomocysteinemia-related gene polymorphisms may contribute to LMCAD susceptibility in a Chinese population. We studied the association between polymorphisms in the genes hepatocyte nuclear factor 1 alpha (HNF1A; rs7310409, G/A), C-reactive protein (rs1800947 and rs3093059 T/C), methylenetetrahydrofolate reductase (rs1801133, C/T), and methylenetetrahydrofolate dehydrogenase (rs1076991, A/G) in 402 LMCAD and 804 more peripheral CAD patients in a Chinese population. Genotyping was performed using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. When the HNF1A rs7310409 GG homozygote genotype was used as the reference group, both the individual, GA and AA, and combined GA/AA genotypes were associated with an increased risk of LMCAD. This single nucleotide polymorphism (rs7310409) is strongly associated with plasma CRP levels. In conclusion, the present study provides evidence that the HNF1A rs7310409 G/A functional polymorphism may contribute to the risk of LMCAD.

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

“…AA genotype of rs2192932 in the MLL5 gene could be protective genetic markers of CAD (Yuan et al 2014). In addition, there is evidence showing that the HNF1A rs7310409 (G/A) functional polymorphism may contribute to the risk of left main CAD (Liu et al 2014d). This study also stated that inflammation was responsible for the initiation and progression of CAD and atherosclerosis.…”

“…Human chromosome 17 is implicated in a wide range of human genetic diseases including early-onset breast cancer (BRCA1), neurofibromatosis (NF1) and the DNA damage response (TP53 encoding the p53 protein) (Zody et al 2006). On this potential genetic foundation, together with the evidence of a potential protective effect of PEDF against CVD or atherosclerosis (Rychli et al 2009;Wang et al 2013;Liu et al 2014d) and the effect of SNP on gene expression (Samnegard et al 2005), we speculate that the observed correlation of this SNP rs8075977 (C/T) with CAD may be due to an influence on PEDF expression. As shown in Bonferroni correction was applied for multiple testing to reduce Type I errors.…”

“…Moreover, a mounting number of susceptibility genes linked to CAD have been reported (O'Donnell et al 2011;Schunkert et al 2011). Recent studies have established a role for single nucleotide polymorphisms (SNPs) in CAD development or prognosis, including the histone-lysine N-methyltransferase mixed lineage leukemia 5 (MLL5) rs12671368 (G/A) and rs2192932 (G/A) polymorphism, the hepatocyte nuclear factor 1 alpha (HNF1A) rs7310409 (G/A) functional polymorphism and the methylenetetrahydrofolate reductase (MTHFR) rs1801133 (C/T) polymorphism Liu et al 2014d;Yuan et al 2014). Numerous genome-wide association studies (GWASs) lead to the identification of several novel loci associated with CAD (McPherson et al 2007;Myocardial Infarction Genetics Consortium 2009;Takeuchi et al 2012;Ichihara et al 2013).…”

Improved Progression-Free Survival in Irinotecan-Treated Metastatic Colorectal Cancer Patients Carrying the HNF1A Coding Variant p.I27L

“…Hepatocyte nuclear factor 1-alpha (HNF1A) is a master hepatic transcriptional regulator that influences the expression of numerous genes critical to liver functions. Consistent with an important role in hepatic functions, HNF1A locus and genetic variations in HNF1A are associated with maturity-onset diabetes of the young (MODY3) ( Yamagata et al, 1996 ), type 2 diabetes ( Holmkvist et al, 2006 ; Voight et al, 2010 ), and coronary artery disease ( Liu et al, 2014 ; Zhou et al, 2017 ). HNF1A also regulates a number of key genes involved in drug metabolism and disposition including UGT and ATP-binding cassette sub-family C member 2 ( ABCC2) expression ( Odom et al, 2004 , 2007 ; Aleksunes et al, 2009 ; Qadri et al, 2009 ; Hu et al, 2014 ).…”

A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting

“…Further study confirmed that asymptomatic siblings of patients with LMCAD have increased risks for future cardiovascular events than healthy siblings of patients with other manifestations of CAD [ 4 ]. Moreover, many studies have identified that several genetic variants were associated with LMCA lesions [ 5 – 9 ].…”