Association of a transcription factor 21 gene polymorphism with hypertension

Abstract

Abstract.Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ 2 test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P= 0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results indicate that rs12190287 (G→C) of TCF21 is a susceptibility locus for hypertension.

Quantitative trait loci mapped for TCF21 binding, chromatin accessibility and chromosomal looping in coronary artery smooth muscle cells reveal molecular mechanisms of coronary disease loci

“…This finding suggested that these QTLs in HCASMC may play an important role in the genetic mechanism of HCASMC mediated disease progression. All of the QTLs showed enrichment for blood pressure and hypertension phenotypes which are highly consistent with known SMC functions, and association of TCF21 with blood pressure have been identified by population studies with multiple racial ethnic groups [19][20][21]. The highly significant enrichment of breast cancer variants in the bQTL category is consistent with TCF21 being a known tumor suppressor and that is dysregulated in breast cancer, but the enrichment of breast cancer variants among the caQTLs and clQTLs is surprising and suggests a similar genomic and genetic architecture between HCASMC and breast cancer risk genes [22].…”

Association of genetic variants with atrial fibrillation

“…Increased sortilin 1 expression leads to enhanced low-density lipoprotein (LDL)-uptake into cells, being associated with decreased plasma LDL-cholesterol, and a lower risk of coronary artery disease (21). Our previous study showed that rs599839 of PSRC1 was associated with myocardial infarction (14), hypertension (22) and dyslipidemia (hyper-LDL-cholesterolemia) (23) in Japanese individuals, with the minor G allele being protective against these conditions. The present study has shown that rs599839 of PSRC1 was associated with AF with the minor G allele representing a risk factor for this condition.…”

TCF21 rs12190287 Polymorphisms Are Associated with Ventricular Septal Defects in a Chinese Population

“…Fujimaki et al (2015) reported that rs12190287 polymorphisms are significantly associated with hypertension in Japanese populations. In the current study, we found that rs12190287 polymorphisms are associated with VSDs in a Chinese population.…”