HDAC9 gene is associated with stroke risk in a Chinese population

Abstract

A recent Genome-Wide Association study (GWAS) identified rs11984041 on HDAC9 gene to be significantly associated with stroke in a Caucasian population. However, whether HDAC9 gene also plays a role in other ethnicities is unknown. The current study was conducted to investigate the association of single nucleotide polymorphisms (SNPs) on HDAC9 gene and stroke risk in a Chinese population. Sixteen tagging SNPs for HDAC9 gene were genotyped in a Chinese population of 279 stroke cases and 984 controls from Changhai Hospital in Shanghai, China. The candidate region of HDAC9 investigated was on a haplotype block located between two recombination hotspots in the tail region of HDAC9, the only region harbouring significantly associated SNPs based on the previous GWAS. rs11984041 was not polymorphic in Chinese population. Two other SNPs, rs2389995 and rs2240419 on HDAC9 of chromosome 7q21.1, were significantly associated with large-vessel stroke risk, with P values of 0.035 and 0.042, respectively (Table 3). Individuals with risk allele (A) for rs2389995 and (T) for rs2240419 had increased risk of stroke (odds ratio [OR] = 1.33, 95% confidence interval [CI]: 1.01-1.75; and OR = 1.29, 95% CI: 1.02-1.63), respectively. Multivariate analysis including both SNPs in the logistic regression model revealed independent association effects of each SNP, with a P = 0.013 and 0.010, respectively. The results from our studies indicate HDAC9 gene is significantly associated with large-vessel stroke risk in Chinese population. However, SNPs on HDAC9 gene display heterogeneity effects across different ethnic populations. Additional studies are needed to further evaluate our results.

Association of GWAS-supported loci rs2107595 in HDAC9 gene with ischemic stroke in southern Han Chinese

“…Thirdly, only one SNP on HDAC9 gene was investigated in the relationship between rs2107595 and stroke, which can not represent all the genetic variants of HDAC9 gene. Moreover, Han et al (2013) have found that the SNP rs2389995 and rs2240419 on HDAC9 were significantly associated with stroke in the Chinese population. Hence, it is necessary that further studies focus on the issue whether rs2107595 can influence the occurrence of stroke by combined effects of the two SNPs in the Chinese population.…”

“…However, the HapMap data show that rs11984041 was not polymorphic in Chinese Han population (HapMap-HCB). A replicated study (Han et al, 2013) indicated that the rs11984041 single nucleotide polymorphism (SNP) was not associated with stroke in Chinese population, while a significant association was found between two other SNPs (rs2389995 and rs2240419) in HDAC9 gene and large-vessel stroke. From this we can see, HDAC9 gene might contain susceptibility loci in stroke risk, and the distribution of genetic polymorphism on the HDAC9 gene may have racial difference in different ethnic populations.…”

“…It is reported that HDAC9 might increase stroke risk (Bellenguez et al, 2012;Han et al, 2013), and a polymorphic loci rs2107595 in HDAC9 gene is identified being associated with the susceptibility of IS Dichgans et al, 2014). Despite great progress in genetics of IS, few underlying genetic variants have been credibly identified in association with the susceptibility of IS until now.…”

Mechanisms and treatment of ischaemic stroke—insights from genetic associations

“…19 This association was replicated in the same study in a further 6,000 patients from Europe, America and Australia, 19 and in subsequent studies. 20,21 The 7p21 locus resides between two recombination hotspots that encompass the 3' end of the histone deacety lase 9 (HDAC9) gene, making it likely that this gene underlies the observed association with large-artery stroke. 19 The variants identified in the WTCCC2 GWAS, and a nearby linked variant that was identified in a subsequent meta-analysis (METASTROKE), 20 are located within the introns of HDAC9 rather than in the coding regions.…”

Polymorphism of HDAC9 Gene Is Associated with Increased Risk of Acute Coronary Syndrome in Chinese Han Population

“…A recent genome-wide association study (GWAS) linked a variant of HDAC9 (rs11984041) on chromosome 7p21.1 with large-vessel ischemic stroke in individuals with European ancestry [8]. Han et al reported that two SNPs, rs2389995 and rs2240419 on HDAC9, were significantly associated with large-vessel ischemic stroke risk in the Chinese population, although rs11984041 was not polymorphic in the Chinese population [9]. Upregulation of HDAC9 expression was observed in human atherosclerotic plaques including in carotid, aortic, and femoral plaques, which appears to implicate the altered HDAC9 expression in promoting atherosclerosis [6, 10].…”