Effect of SNP Polymorphisms of EDN1, EDNRA,and EDNRB Gene on Ischemic Stroke

The objective of this study is to investigate the association between SNP polymorphisms of endothelin-1 (EDN1) and endothelin receptor (EDNRA and EDNRB) gene and ischemic stroke (IS) in the Chinese Han population in northern. A case–control study was introduced. We genotyped eight SNPs (rs1800541, rs2070699, and rs5370 in EDN1 gene; rs1801708, rs5333, and rs5335 in EDNRA gene; and rs3818416 and rs5351 in EDNRB gene) and calculated their polymorphic distribution in control group, IS group, and the IS subgroups. In male population, EDN1 gene rs2070699 G allele increased the incidence risk to 1.78 times (P = 0.009; OR 1.78; 95 % CI 1.15–2.75) and the risk of morbidity of rs5370 T allele carrying increased to 1.49 times (P = 0.048; OR 1.49; 95 % CI 1.00–2.21). EDNRA gene mutation rs5335 homozygous CC morbidity risk was significantly lower (P = 0.016; OR 0.52; 95 % CI 0.31–0.88). In the female population, the mutant homozygous AA cancer risk was significantly higher than G allele carriers (P = 0.019; OR 2.65; 95 % CI 1.18–6.00) on EDNRA gene rs1801708. In EDN1 gene, T allele of rs5370 and G allele of rs2070699 may be IS incidence risk factors in Northern Han male population. A allele of rs1801708 in EDNRA gene can increase the risk of IS in Northern Han women population.     

miR-146a and miR-196a2 Polymorphisms in Patients with Ischemic Stroke in the Northern Chinese Han Population

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3′-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case–control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199–2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery athersclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.     

Assessment of association of rs2200733 on chromosome 4q25 with atrial fibrillation and ischemic stroke in a Chinese Han population

Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting and an independent risk factor for stroke. Approximately 10 million Chinese people are affected by AF, but the genetic basis is largely unknown. A recent genome-wide association study in Iceland identified association between SNP rs2200733 on 4q25 and AF; however, many independent replication studies are essential to unequivocally validate this association. To assess the association between rs2200733 and AF as well as that between rs2200733 and ischemic stroke in a mainland Chinese Han population, we carried out case–control association studies with 383 AF patients versus 851 non-AF controls and 811 ischemic stroke patients versus 688 non-stroke controls. Highly significant association was detected between rs2200733 and AF in a Chinese Han population (allelic P = 3.7 × 10^?11 with OR = 1.81; genotypic P = 4.1 × 10^?12 with a dominant model). When the AF cases were divided into lone AF (32.6%) and other types of AF (67.4%), significantly stronger association was found with lone AF (OR = 2.40, P = 1.3 × 10^?9 compared to OR = 1.59, P = 6.2 × 10^?7 for other types of AF; P = 0.02 for two ORs). No significant association was found between rs2200733 and ischemic stroke. Our results suggest that SNP rs2200733 confers a highly significant risk of AF, but not ischemic stroke, in a more representative Chinese Han population in the mainland China.     

BRG1 variant rs1122608 on chromosome 19p13.2 confers protection against stroke and regulates expression of pre-mRNA-splicing factor SFRS3

A single nucleotide polymorphism (SNP) rs1122608 on chromosome 19p13.2 and in the BRG1/SMARCA4 gene was previously associated with coronary artery disease (CAD). CAD and ischemic stroke are both associated with atherosclerosis. Thus, we tested the hypothesis that rs1122608 is associated with ischemic stroke. Further studies were used to identify the most likely mechanism by which rs1122608 regulates atherosclerosis. For case–control association studies, two independent Chinese Han GeneID cohorts were used, including a Central cohort with 1,075 cases and 2,685 controls and the Northern cohort with 1,208 cases and 824 controls. eQTL and real-time RT-PCR analyses were used to identify the potential candidate gene(s) affected by rs1122608. The minor allele T of SNP rs1122608 showed significant association with a decreased risk of ischemic stroke in the Central GeneID cohort (adjusted P _adj = 2.1 × 10^?4, OR 0.61). The association was replicated in an independent Northern GeneID cohort (P _adj = 6.00 × 10^?3, OR 0.69). The association became more significant in the combined population (P _adj = 7.86 × 10^?5, OR 0.73). Allele T of SNP rs1122608 also showed significant association with a decreased total cholesterol level (P _adj = 0.013). Allele T of rs1122608 was associated with an increased expression level of SFRS3 encoding an mRNA splicing regulator, but not with the expression of BRG1/SMARCA4 or LDLR (located 36 kb from rs1122608). Increased expression of SFSR3 may decrease IL-1β expression and secretion, resulting in reduced risk of atherosclerosis and stroke. This is the first study that demonstrates that rs1122608 confers protection against ischemic stroke and implicates splicing factor SFSR3 in the disease process.     

Polymorphisms of ECE1 May Contribute to Susceptibility to Ischemic Stroke in Han Chinese of Northern China

Endothelin (ET) converting enzyme 1 (ECE1) is well known for its critical role in the process of ET. Recent studies have demonstrated that two genetic variants of ECE1 gene, rs212528 and rs213045 (C338A), are associated with hypertension and atherosclerosis formation. To investigate the association between the ECE1 gene polymorphisms and ischemic stroke (IS) in Chinese population. With a candidate loci strategy, we conducted a case–control study involving 381 IS cases and 366 non-IS controls in Han population of the Northern China. Two single nucleotide polymorphisms of ECE1 were genotyped and assessed the association with the risk of IS. Furthermore, stratified analyses were also carried out to evaluate the association between the gender or two etiologic subtypes [small-artery occlusion (SAO) and large-artery atherosclerosis (LAA)] and IS. Compared with rs213045 G homozygote, rs213045 TG genotype and rs213045 TT/TG genotypes are in dominant model significantly increased the risk of IS [adjusted odds ratio (OR) = 1.47, 95 % confidence interval (CI) = 1.04–2.07, P = 0.03; adjusted OR = 1.43, 95 % CI = 1.04–1.99, P = 0.029, respectively]. However, we did not find the significant association between the ECE1 gene polymorphisms and SAO or LAA of IS in this study. Our results indicated that ECE1 gene polymorphisms may contribute to the susceptibility of IS in Han population of the Northern China.     

Association of adiponectin gene polymorphisms with the risk of ischemic stroke in a Chinese Han population

Adiponectin is inversely associated with the risk of ischemic stroke through its anti-inflammatory and anti-atherogenic effects. Genetic variations in the adiponectin gene (ADIPOQ) have been shown to be associated with the risk of ischemic stroke in Caucasians and Japanese populations. However, it was unknown whether variations in the ADIPOQ gene were associated with the risk of ischemic stroke in Chinese population. A case-control study was performed among 302 patients with ischemic stroke and 338 unrelated controls in a Chinese Han population. The single-nucleotide polymorphisms (SNPs) rs266729 (−11377C/G), rs2241766 (+45T/G), rs1501299 (+276G/T) in the ADIPOQ gene were genotyped by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GG genotype and G allele of rs266729 in the patients with ischemic stroke were significantly higher than those in the controls (P = 0.034, P = 0.010, respectively). In univariate logistic analysis, compared with CC genotype, GG genotype of rs266729 increased the risk of ischemic stroke (odds ratio (OR) = 2.062, 95% confidence interval (CI) = 1.145–3.715, P = 0.016). After adjustment for potential risk factors by the multivariate logistic analysis, rs266729 remained positive correlation with ischemic stroke (OR = 2.165; 95% CI = 1.116–4.197, P = 0.022). However, no significant association was observed among rs2241766, rs1501299 and ischemic stroke. In addition, no significant difference was found in haplotype frequencies between the patients with ischemic stroke and control subjects. The present study demonstrated that the promoter polymorphism rs266729 of the ADIPOQ gene was associated with an increased risk of ischemic stroke in the Chinese Han population.     

A novel major histocompatibility complex locus confers the risk of premature coronary artery disease in a Chinese Han population

Several novel loci have been proved to be associated with coronary artery disease and/or myocardial infarction risk by genome-wide association studies, however, the available coronary artery disease risk variants explain only a small proportion of the predicted genetic heritability of the disease. Recently, a novel coronary artery disease locus on chromosome 6p21.3 in the major histocompatibility complex was identified in an European population. We hereby investigated whether this single nucleotide polymorphisms (rs3869109) confers the risk of premature coronary artery disease in a Chinese Han population. A total of 422 patients were studied including 210 cases with coronary stenosis ≥50 % or previous myocardial infarction (male <55 years and female <65 years) and 212 controls without documented coronary artery disease. Ligase detection reaction was performed to detect rs3869109. The 3 genotypes AA, AG, and GG were present in rs3869109. There were significant differences between the control and premature coronary artery disease groups in the frequencies of the rs3869109 variants and alleles (all P < 0.05). The distribution of 3 genotypes and alleles at rs3869109 does not differ between women and men (all P > 0.05). There was a significant association between rs3869109 genotypes and the severity of premature coronary artery disease (P = 0.038). Multivariate logistic regression showed that carriers with AG and GG genotypes at rs3869109 have a higher risk of premature coronary artery disease than carriers of AA genotype (odds ratio [OR] 1.997, 95 % CI: 1.166–3.419, P = 0.012; OR 1.695, 95 % CI: 1.044–2.752, P = 0.033; respectively). Our results indicate that the rs3869109 variants are associated with premature coronary artery disease in a Chinese Han population, suggesting this genetic risk marker is useful in early coronary artery disease risk prediction.     

Association of the apolipoprotein M gene polymorphisms and serum lipid levels

The association of rs707921 and rs707922 SNPs in the apolipoprotein M (APOM) gene and serum lipid levels is still controversial. This study aimed to detect the association of the APOM rs707921 and rs707922 SNPs and several environmental factors with serum lipid profiles. Genotyping of rs707921 and rs707922 was performed in 703 of Mulao’s and 707 of Han’s participants. The serum levels of TG in Mulao, and TG and HDL-C in Han were different between the A and C allele carriers of rs707921 (P < 0.05–0.01); while the serum levels of TG in both Mulao and Han were different between the T and G allele carriers of rs707922 (P < 0.05–0.01). According to the gender-subgroup analysis, the levels of TC in Mulao females, TG and ApoB in Han males, and HDL-C in Han females were associated with the genotypes of rs707921 (P < 0.05 for each); whereas the levels of TG in Mulao males, and TG and ApoB in Han males were correlated with the genotypes of rs707922 (P < 0.05 for each). Serum lipid parameters were also associated with several environmental factors (P < 0.05–0.001). The APOM gene rs707921 and rs707922 SNPs are associated with some serum lipid parameters in the two ethnic groups, but the trends of association suggest that the two SNPs might have racial/ethnic- and/or gender- specificity.     

Age-dependent association of KIBRA gene polymorphism with Alzheimer’s disease in Han Chinese

Genetic factors play an important role in the Alzheimer’s disease (AD) development and memory impairment is a cardinal clinical feature of AD. Kidney and brain expressed protein (KIBRA), owing to its connection with human episodic memory, became an interesting candidate gene for AD. Recently, KIBRA (rs17070145) was reported to be associated with AD in the genetic and functional levels in Caucasian and African-American, and the association might be different across age groups. To investigate the possibility of age-dependent association of KIBRA with AD in Asian, we conducted an independent replication study in a cohort of 1,586 subjects from Han Chinese (including 790 LOAD patients and 796 healthy controls). The results revealed no significant differences in the distributions of genotype or allele between LOAD and control groups in the total sample. However, when these data were stratified by their age, we observed a significant difference in the genotypes and alleles frequencies (genotype: p = 0.004, allele: p = 0.035) in the young subgroup. Moreover, the association was further demonstrated in logistic regression analysis (rs17070145: p = 0.045, OR = 0.428). Our data suggested that KIBRA might associate with younger AD patients (≤74 years) in a Northern Han Chinese population.     

Association of two variants in the interleukin-6 receptor gene and premature coronary heart disease in a Chinese Han population

Two novel single nucleotide polymorphisms (SNPs; rs7529229 and rs2228145) in the interleukin-6 receptor (IL6R) gene have recently been associated with coronary heart disease (CHD) in a European population. We sought to replicate this finding and to investigate associations of these two SNPs with the severity and clinical phenotypes of premature CHD in a Chinese Han population. A total of 418 patients were studied, including 187 cases with coronary stenosis ≥50 % or acute myocardial infarction (males < 55 years and females < 65 years) and 231 controls without documented CHD. A ligase detection reaction was performed to detect rs7529229 and rs2228145. There were no differences between the controls and premature CHD groups in the frequencies for the three genotypes and alleles of rs7529229 and rs2228145 (all P > 0.05), nor did they differ between the two groups when grouped by gender (all P > 0.05). There were also no associations between these two SNPs and the severity of coronary lesions or clinical phenotypes of premature CHD (all P > 0.05). Our results do not support an association between rs7529229 or rs2228145 with premature CHD in the Chinese Han population. Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD.     

Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes

The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. Five hundred and seventy-seven patients with type 2 diabetes and 462 normal controls were enrolled in this study. Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan^® technology. Single-locus analyses indicated that the C allele of rs11574736 from HNF4A had a lower frequency in the case group compared with the control group (P = 0.005, OR = 0.74, 95% CI = 0.59–0.92). The genotype distributions of rs11574736 also differed between the two groups (P = 0.02). However, none of the FOXO1 SNPs showed any association with type 2 diabetes in the Chinese Han population. Further analysis suggested the two genes interact with each other (rs3908773/rs717247/rs6031587/rs11574736: P < 0.0001, testing accuracy = 0.55, CV consistency = 6/10). In conclusion, this study shows an association between the HNF4A gene and type 2 diabetes in the Chinese Han population. Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes.     

SORL1 Is Associated with the Risk of Late-Onset Alzheimer’s Disease: a Replication Study and Meta-Analyses

The sorting-related receptor gene (SORL1) has been defined as an interesting candidate gene for Alzheimer’s disease (AD). Recently, one novel variant, rs11218343, within SORL1 was reported to be related to late-onset Alzheimer’s disease (LOAD) in Caucasians, Korean, and Japanese. The aim of this case–control study is to investigate whether SORL1 rs11218343 contributes to susceptibility for LOAD in Chinese. Furthermore, our data, along with previously studies, were pooled for determining the risk of the rs11218343 polymorphism on LOAD. The rs11218343 polymorphism was genotyped in the 2350 independent subjects from Northern Han Chinese population (including 992 cases and 1358 age- and gender-matched controls). Result of the case–control study showed the association between rs11218343 polymorphism and the risk of LOAD in a Northern Han Chinese population (recessive model: odds ratio (OR)?=?0.641, 95 % confidence interval (CI)?=?0.464–0.884, P?=?0.007; additive model: OR?=?0.873, 95 % CI?=?0.765–0.996, P?=?0.043). The results of meta-analysis in subgroups (Caucasian and Asian) and the whole showed that the minor allele (C allele) within rs11218343 played a protective effect on AD risk (OR (95 % CI), 0.77 (0.72–0.83), 0.85 (0.79–0.91), 0.81 (0.76–0.85), respectively). In conclusion, the C allele in SORL1 rs11218343 may be a protective factor for LOAD in both Caucasian and Han Chinese.     

The association between a single nucleotide polymorphism rs11966200 in MHC region and clinical features of generalized vitiligo in Chinese Han population

Vitiligo is an acquired pigmentary disorder characterized by loss of epidermal melanocytes. A strong association at a single nucleotide polymorphism (SNP) rs11966200 within MHC region had been identified in a recent genome-wide association study of generalized vitiligo in Chinese Han population. This study aims to investigate the relationships between SNP rs11966200 and the clinical features of generalized vitiligo in Chinese Han population. We compared the allele and genotype frequency among different vitiligo subphenotypes including age onset, extent of disease, clinical subtypes, family history of vitiligo and history of autoimmune disease. Our data showed SNP rs11966200 was associated with early-onset vitiligo (onset age ≤20 years) (odds ratio [OR], 1.54; p = 2.01 × 10^?13), moderate-severe vitiligo (involved body surface ≥5 %) (OR, 1.17; p = 0.025), vitiligo vulgaris (OR, 1.13; p = 0.043), and focal vitiligo (OR, 0.86; p = 0.018). The study suggested that the underlying risk causal allele tagged by SNP rs11966200 might not only play important roles in the development of vitiligo, but also contribute to the diverse clinical characteristics of generalized vitiligo at least in Chinese Han population.     

Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p?<?1?×?10^?8) and rs17118 in XYLB gene located on chromosome 3p21 (p?<?1?×?10^?6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR?=?2.02, 95 % CI?=?1.35–3.03) or rs17118 AA genotype (OR?=?1.50, 95 % CI?=?1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR?=?2.78, 95 % CI?=?1.59–4.86) and in individuals without diabetes (OR?=?1.93, 95 % CI?=?1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR?=?1.73, 95 % CI?=?1.08–2.78) and for individuals without diabetes (OR?=?1.52, 95 % CI?=?1.17–1.98) or non-smoker (OR?=?1.59, 95 % CI?=?1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.     

Association study of common variations of FBN1 gene and essential hypertension in Han Chinese population

Fibrillin-1 (FBN1) was reported to have impact on the physiological arterial stiffness and vascular remodeling with hypertension of recent years. In the previous study we reported the association of four functional single nucleotide polymorphisms (SNPs) of FBN1 gene and hypertension. Here, we further investigate the association of four tagging SNPs (tagSNPs) which covered remain genetic variation blocks of FBN1 gene with hypertension, blood pressure and efficacy of antihypertensive in a South Han Chinese population. A case–control study including 2,012 hypertension cases and 2,116 controls age- and sex-matched controls was conducted from a community-based population and four candidate tagSNPs of the FBN1 gene were genotyped. Association analysis by multiple logistic regression was conducted for allele, genotype and haplotype and hypertension, blood pressure trait and control status with antihypertensive. General linear model was applied to compare blood pressure levels between genotypes. The association of rs17361868 and hypertension was statistically significant and that was further observed in female, ≥55 years, non-smoking and non-drinking populations (P < 0.05). Significant association of rs668842, rs11635140 and hypertension were observed in <55 years population as well as the later in female and non-smoking populations respectively. Haplotype G-T constructed of rs668842 and rs11635140 was significantly associated with hypertension comparing to reference haplotype A-C (P = 0.022). Normally distributed square root of TGF-β1 (pg/ml) of hypertension cases (148.56 ± 66.46) was significantly higher than that of control (128.52 ± 65.11), P = 0.008. Furthermore, TGF-β1 was significantly correlated with SBP (r = 0.135, P = 0.018) and DBP (r = 0.154, P = 0.007) respectively whereas no statistical difference of blood pressure or TGF-β1 was observed between genotypes. Remarkably, rs17361868 were significantly associated with the status of blood pressure in the patients taking three of the antihypertensive drugs, Zhen Ju Jiang Ya tablets, Jiang Ya tablet and compound reserpine (P < 0.05). The present study provides further association evidence of FBN1 gene polymorphisms and hypertension, antihypertensive efficacy. Further replication of these results via association or prospective studies conducted in other populations is warranted.     

KCNQ1 and type 2 diabetes: study in Hubei Han Chinese and meta-analysis in East Asian populations

Recent genome-wide association studies in East Asian poulations reported the association of KCNQ1 variants with type 2 diabetes. In the present study, we first investigated the association between rs2237892 in KCNQ1 and type 2 diabetes in a Hubei Han Chinese population (223 type 2 diabetes patients and 201 controls). The frequencies of CC genotype and C allele in type 2 diabetes patients were significantly higher than those of controls group (CC: 51.6% vs 39.3%, P=0.001; C: 72.2% vs 61.2%, P=0.001). The odds ratio for the risk allele C was 1.65 (95%CI 1.23–2.2, P=0.001). Then, we systematically reviewed the association of SNPs (rs2237892, rs2237895, rs2237897, rs2074196) in KCNQ1 with type 2 diabetes risk in a meta-analysis. Significant heterogeneity between studies was found for SNPs rs2237892 and rs2237897. Combined odds ratios of the rs2237892 C, rs2237895 C, rs2237897 C, rs2074196 G allele were 1.35 (95% CI 1.29–1.41, P<0.0001), 1.27 (95%CI 1.23–1.32, P<0.0001), 1.32 (95%CI 1.21–1.43, P<0.0001), 1.30 (95%CI 1.25–1.35, P<0.0001) respectively. Our results and meta-analysis demonstrated that KCNQ1 polymorphisms were reproducibly associated with the risk of type 2 diabetes in Han Chinese and East Asian populations.     

Kalirin: a novel genetic risk factor for ischemic stroke

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1–KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.     

Genetic Association of rs1800780 (A→G) Polymorphism of the eNOS Gene with Susceptibility to Essential Hypertension in a Chinese Han Population

To investigate the association of eNOS gene polymorphism with essential hypertension in the Chinese Han population, we examined polymorphisms of the rs2070744 (T→C), rs1800780 (A→G), and rs3918181 (A→G) loci. The results demonstrated that the genotypic frequency at the rs1800780 (A→G) locus was significantly different between patients with essential hypertension and the control cohorts (P < 0.05); while genotypic frequencies and allelic frequencies at rs2070744 (T→C) and rs3918181 (A→G) loci had no statistical difference between the patient group and controls (P > 0.05). In addition, haplotype analysis found a statistically significant difference for haplotype TGA, with OR (95% CI) of 1.549 (1.116–2.150) (P < 0.05). These findings suggest that polymorphism of rs1800780 (A→G) in the eNOS gene may be one of the most important genetic factors associated with essential hypertension susceptibility, and those who have haplotype TGA may be at risk to develop essential hypertension.