Influence of prenatal iron deficiency and MAOA genotype on response to social challenge in rhesus monkey infants

Social and emotional behaviors are known to be sensitive to both developmental iron deficiency (ID) and monoamine oxidase A (MAOA) gene polymorphisms. In this study, male rhesus monkey infants deprived of dietary iron in utero were compared with iron sufficient (IS) controls (n = 10/group). Half of each group had low MAOA activity genotypes and half had high MAOA activity genotypes. A series of social response tests were conducted at 3-14 months of age. MAOA genotype influenced attention to a video of aggressive behavior, emotional expression (fear, grimace and sniff) in the social intruder test, social actions (displacement, grooming) in the social dyad test, and aggressive responses to a threatening picture. Interactions between MAOA and prenatal ID were seen in response to the aggressive video, in temperament ratings, in affiliative behavior in the social dyad test, in cortisol response in the social buffering test and in response to a social intruder and to pictures with social and nonsocial themes. In general, the effects of ID were dependent on MAOA genotype in terms of both direction and size of the effect. Nutrition/genotype interactions may shed new light on behavioral consequences of nutritional deprivation during brain development.     

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.     

Endothelial nitric oxide (eNOS) gene G894T and VNTR polymorphisms are closely associated with the risk of ischemic stroke development for Asians: meta-analysis of epidemiological studies

Although the relationships between endothelial nitric oxide synthase (eNOS) gene polymorphisms (including G894T, VNTR and T786C) and risk of ischemic stroke (IS) have been extensively studied, controversial results have been reported. The aim of this study was to assess the relationships between them by using a meta-analysis. Literatures were retrieved through the following databases: Medline, Embase and Wangfang (updated to January 1st, 2013). Fixed- or random-effects model was used to calculate pooled odds ratio and 95 % confidence interval (OR and 95 % CI). A total of 31 case–control studies including 8,547 patients and 9,117 controls were included in this meta-analysis eventually. For eNOS G894T polymorphism, the results indicated that TT genotype was significantly associated with increased risk of IS incidence compared to G allele (OR and 95 % CI 1.25 (1.09–1.42) for TT vs. GT+GG, P < 0.001). When subgroup analysis was conducted according to ethnicities, T allele was significantly associated with risk of IS for Asians rather than for Caucasians. For eNOS VNTR polymorphism, 4aa genotype was significantly associated with risk of IS incidence compared to 4bb genotype (OR (95 % CI) 2.22 (1.66–2.97) for aa vs. bb, P < 0.001). Similarly, when subgroup analyses were conducted, 4aa was closely associated with increased risk of IS for Asians rather than for Caucasians. For eNOS T786C polymorphism, it was not associated with risk of IS incidence. In conclusion, this study indicated that eNOS 894T and VNTR 4a allele was significantly associated with risk of IS incidence for Asians. However, eNOS T786C polymorphism was not a likely risk factor for IS incidence.     

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30–40 days of age, pre-pubertal period) of 40–50 g body weight were divided into the following: the ZC (zinc control) group—fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group—fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group—received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.     

A Polymorphism Within the 3′UTR of <Emphasis Type="Italic">NLRP3</Emphasis> is Associated with Susceptibility for Ischemic Stroke in Chinese Population

Stroke was regarded as a severe disorder with high morbidity and high mortality worldwide, ischemic stroke (IS) accounts for 85 to 90 % of new increased stroke cases. Partial mechanisms were elucidated by genetic factors including genomic instability such as single nucleotide polymorphism (SNP). Previous reports demonstrated that inflammation was involved in IS, NLRP3 [nucleotide-binding domain (NOD)-like receptor protein 3], acting as a specific inflammatory gene, however, its function and influence on IS was not well clarified. In this study, a case–control study including 1102 IS patients and 1610 healthy controls was conducted to investigate the association between IS susceptibility with a SNP (rs10754558) in 3′UTR of NLRP3. Logistic regression analysis showed that the heterozygote and the homozygote GG confer a significantly increased risk of CRC after controlling for other covariates (adjusted OR = 1.52, 95 % C.I. 1.19–1.97, P = 0.002; adjusted OR = 2.22, 95 % C.I. 2.18–3.67, P < 0.001, respectively). Carriage of G allele was associated with a greatly increased risk of developing the disease (OR = 1.69, 95 % C.I. 1.31–1.83, P < 0.001). Stratification analysis found that hypertension had interaction with rs10754558 to modulate IS risk. Further in vitro assay revealed that rs10754558 can affect mRNA level of NLRP3, suggesting its possible functional significance. Our data suggested that genetic polymorphisms in NLRP3 may influence IS risk in Chinese population. Replication of our studies in other populations and further functional studies are required for complete comprehension of the roles of NLRP3 polymorphisms in IS risk.     

Sequence variation in promoter regions of genes for CC chemokine ligands (CCL)19 and 21 in Czech patients with myocardial infarction

Recruitment of inflammatory cells to the arterial wall is an important pathogenic mechanism of atherosclerosis and coronary artery disease (CAD). Functional variability in the genes encoding for chemokines that promote infiltration of atherosclerotic plaques by macrophages and lymphocytes may therefore contribute to the genetic susceptibility to CAD. We, therefore, investigated the association between myocardial infarction (MI) and polymorphisms in the promoter regions of the chemokine genes CCL19 and CCL21. Based on re-sequencing screening we selected and, using PCR-SSP, determined three polymorphisms of CCL19 gene (GenBank ID rs2233872) and CCL21 gene (GenBank ID rs11574914 and rs11574915) in 211 Czech patients with MI and 150 healthy control subjects. There was no difference in allelic frequencies of the investigated SNPs between patients and controls (p > 0.05). However, the proportion of homozygotes for the minor G allele of the CCL21 promoter variant (rs11574915 GG) was lower among the MI patients (1 %) in comparison with the control subjects (5 %, nominal p = 0.03). Though rare in the Czech population, CCL21 (rs11574915) GG genotype may confer protection from myocardial infarction. Our preliminary data have to be independently replicated.     

Seed Priming with Iron Oxide Nanoparticles Triggers Iron Acquisition and Biofortification in Wheat (Triticum aestivum L.) Grains

Iron deficiency anaemia is a major challenge among consumers in developing countries. Given the deficiency of iron in the diet, there is an urgent need to devise a strategy for providing the required iron in the daily diet to counter the iron deficiency anaemia. We propose that iron biofortification of wheat (Triticum aestivum L.) through seed priming would be an innovative strategy to address this issue. This investigation attempts to find the interaction of iron oxide nanoparticles on germination, growth parameters and accumulation of grain iron in two contrasting wheat genotypes WL711 (low-iron genotype) and IITR26 (high-iron genotype). Wheat seeds were primed with different concentrations of iron oxide nanoparticles in the range of 25–600 ppm, resulting in differential accumulation of grain iron contents. We observed a pronounced increase in germination percentage and shoot length at 400 and 200 ppm treatment concentrations in IITR26 and WL711 genotypes, respectively. Intriguingly, the treatment concentration of 25 ppm demonstrated higher accumulation with a significant increase in grain iron contents to 45.7% in IITR26 and 26.8% in WL711 genotypes, respectively. Seed priming represents an innovative and user-friendly approach for wheat biofortification which triggers iron acquisition and accumulation in grains.

     

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.     

MTHFR Polymorphisms Involved in Vitamin B12 Deficiency Associated with Atrophic Gastritis

Genetic polymorphisms affecting methylentetrahydrofolate reductase (MTHFR) activity may influence hematological and neurological dysfunction in cobalamin-deficient patients. We studied the prevalence of C677T and A1298C polymorphisms by analyzing genomic DNA in 30 cobalamin-deficient patients. No significant difference was found in 677 and 1298 genotype distribution with respect to hematological parameters, B₁₂ and folate levels, and neurological symptoms. The two MTHFR polymorphisms were not protective against anemia or neurological dysfunction in patients with cobalamin deficiency; however, we found evidence of a significant increase in atrophic gastritis in the 677TT group (P = 0.009) but not for the 1298CC genotype. Based on observations that inadequate cobalamin intake and reduced MTHFR activity might be significant risk factors for gastric cancer, and the increased risk of gastric cancer shown in patients affected by atrophic gastritis, we speculate that concomitant atrophic gastritis and impaired MTHFR function could have a role in the development of gastric cancer.     

Oxidative effect of several intravenous iron complexes in the rat

The objective of this study was to compare the oxidative stress induced in rat internal organs by the administration of the following clinically used intravenous (IV) iron (Fe) containing compounds: iron sucrose (IS), iron dextran (ID), ferric carboxymaltose and ferumoxytol. Groups of six adult rats received 1 mg/kg of each compound weekly for 5 doses. Seven days following the last dose, animals were euthanized and tissue samples of heart, lung, liver, and kidney were obtained, washed in warmed saline and frozen under liquid nitrogen and stored at ?80 °C for analysis for nitrotyrosine (NT) and dinitro phenyl (DNP) as markers of oxidative stress. All tissues showed a similar pattern of oxidative stress. All Fe products stimulated an increase in the tissue concentration of both NT and DNP. In general, DNP was stimulated significantly less than NT except for IS. DNP was stimulated to an equal degree except for ID where NT was significantly higher than the NT concentrations in all other Fe compounds. ID produced over 10-fold the concentration of NT than any other Fe. IV Fe compounds present a risk of oxidative stress to a variety of internal organs. However, we found that IS was the least damaging and ID was the worst.     

Temporal kinetics of fluoride accumulation: from fetal to adult deer

In June 2011, a volcano deposited about 100 million tons of tephra over parts of Chile and over 36 million ha of Argentina. Initially, fluoride was considered irrelevant; however, recently wild deer exhibited strong fluorosis, with fluoride level increasing 38-fold among severely affected deer. Whereas mothers averaged 2,151 ppm, their late-term fetuses had only 19.8 ppm, indicating a barrier to fluoride transport in utero. Levels among four age classes increased significantly, at a rate of about 1,000 ppm/year. The temporal kinetics of accumulation suggests that sources of available fluoride are highly effective. Thus, compared to prior background levels (63 ppm in adults) and to fetuses starting at about 20 ppm, 1-year-old calves averaged 1,035 ppm (maximum 1,830 ppm), 2-year olds averaged 2,151 ppm (maximum 2,513 ppm), and older deer averaged 2,806 ppm (maximum 5,175 ppm). As osteofluorosis occurs in deer with >4,000 ppm, accumulation of 1,000 ppm/year would result in adults reaching levels causing osteopathology in 1–2 years. Importantly, impacts may be further exacerbated by regional iodine and selenium deficiencies. Iodine deficiency may increase incidences of dental fluorosis and severity of damages, while selenium deficiency impacts iodine metabolism. Fluorosis will affect population dynamics, morbidity, predation susceptibility, and other ecosystem components like scavenger and plant communities.     

MAOA, MTHFR, and TNF-β genes polymorphisms and personality traits in the pathogenesis of migraine

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.     

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.     

Effect of ID ACE gene polymorphism on dietary composition and obesity-related anthropometric parameters in the Czech adult population

The aim of this study was to investigate the possible associations between insertion/deletion (ID) polymorphism in angiotensin-converting enzyme (ACE) (dbSNP rs 4646994) with the food intake and body composition in the Czech non-obese, obese and extremely obese populations. A total of 453 various-weighted individuals were enrolled in the study and were according to their BMI assigned into following subgroups, such as obese (30 ≤ BMI < 40), morbidly obese (BMI ≥40) and non-obese (20 < BMI < 30) subjects. Both the obese cases and the non-obese controls underwent the identical subset of standardized examinations (BMI, % body fat, waist-to-hip ratio, skin fold thickness, native dietary composition examined by 7-day food records, etc.). No significant case–control differences in genotype distributions or allelic frequencies were observed. There were no differences in genotype frequencies between males and females either. The prevalence of obesity was significantly higher among subjects with the II genotype (42 %) when compared with those with DD (36%) and those with ID (37%) genotypes (P = 0.04). When compared with carbohydrate intake in the whole studied cohort, the odds ratios of carrying the DD allele in the morbidly obese cohort were 0.84 (95% CI 0.34, 2.10, P = 0.17), 0.27 (0.07, 0.98, P = 0.02), and 4.25 (1.44, 12.51, P = 0.005) in those individuals consuming <210, 210–260, and >260 g of carbohydrates/day, respectively. Based on our findings, the ID ACE polymorphism could represent a gene modulator of carbohydrate intake in morbidly obese Czech population; the strong significant effect of DD genotype was observed in the phenotypes of extreme obesity with the highest carbohydrate intake.     

Association study between the dopamine-related candidate gene polymorphisms and ADHD among Saudi Arabia population via PCR technique

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders characterized by inattention, hyperactivity and impulsivity. In Saudi Arabia the prevalence of combined ADHD is 16.4?%. ADHD etiology is not clear and not completely understood. There are several evidences for involvement of dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters. Dopamine Transporter 1 (DAT1) plays an important role in controlling blood levels of dopamine. The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30?bp-promoter VNTR and DAT1 40?bp 3′ UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95?% confidence interval (95?% CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P?<?0.01, OR?=?3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P?<?0.01, OR?=?2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P?<?0.01, OR?=?4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis. This is the first report investigated the association between MAOA and DAT1 polymorphism at molecular level in Saudi Arabia population as well as Arab world. Therefore further studies are needed to generalize obtained results at Saudi Arabia.     

Effect of Single Nucleotide Polymorphisms of Toll-Like Receptor 4 (TLR 4) on Reproductive Performance and Immune Function in Dairy Cows

In dairy cows, inflammatory diseases caused by infection with pathogenic bacteria post calving affect ovarian functions. This study examined the relationship between single-nucleotide polymorphisms (SNPs) of Toll-like receptor 4 (TLR4), reproductive performances [the number of artificial insemination (AI) application and days open], and immune cell functions (apoptosis and migration). Two hundred Holstein cows from the Obihiro University farm were included. The SNPs of TLR4 were genotyped by PCR-restriction fragment length polymorphism (PCR–RFLP) method. Polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. The number of AI application in the animals with T/C genotype in the TLR4 exon3 was lower than that in animals with C/C genotype (1.6 ± 0.2 and 2.2 ± 0.2, respectively). Among the animals with TLR4 exon3 polymorphisms, the days open was shorter for the T/C cows than that for C/C cows (100.7 ± 6.9 days and 136.6 ± 9.0 days, respectively). The SNPs in the TLR4 intron did not affect the number of AI and days open. The apoptosis percentage of PMNs treated with lipopolysaccharide (LPS; 0.001 and 1 μg/ml) tended to be lower in the T/C genotype compared to that in the C/C genotype. The transmigration rates of PMNs, and IL-1β production in PBMCs were tended to be higher for the animals with the T/C genotype compared to those for animals with the C/C genotype. Taken together, these results suggest that TLR4 polymorphisms offer a meaningful tool to judge the reproductive potential and immune activity in individual cows.     

The Per2 polymorphism rs10462023 is associated with the risk of stroke in a Chinese population

The key clock protein Period2 (Per2) has been suggested to play an essential role in regulating endothelial function. It also regulates the expression of plasminogen activator inhibitor-1, but its role in stroke development has not been studied. To explore the possible association between Per2 and ischemic stroke (IS), 479 Chinese IS patients and 306 healthy controls were recruited, and five tag single nucleotide polymorphisms representing the Per2 locus were genotyped using the Sequenom MassARRAY system. A significant difference was observed in the genotypic distribution (p = 0.014) and allele frequency (p = 0.005) of rs10462023, with carriers of the G allele being more prone to developing IS. After adjusting for possible risk factors including smoking, alcohol use, and history of hypertension and diabetes, a significant association was still apparent. Haplotype analysis also supported the association between Per2 and IS. This study suggests that Per2 variations are associated with IS and may represent genetic risk factors for IS in a Chinese population.