Association of OX40L Polymorphisms with Sporadic Breast Cancer in Northeast Chinese Han Population

OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype A_rs844648A_rs10912580 was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.     

Human genetic evidence that OX40 is implicated in myocardial infarction

We recently showed that genetic variants in OX40L are associated with myocardial infarction (MI) and severity of coronary artery disease in human. A number of studies also suggest a possible role for OX40 (the OX40L receptor) as a factor contributing to atherosclerosis. In the present study, the OX40 gene was screened for variants associated with precocious MI, using individuals with MI before the age of 60 and controls. Despite the fact that the OX40 gene is highly conserved between species and that relatively few common genetic variants were encountered, an association with MI was seen for a polymorphism in intron 5 (rs2298212). In silico investigation suggested that genetic variation (rs2298211), linked to this intronic variant, is possibly affecting spliceosome function. Our results provide evidence that variants in human OX40 might influence susceptibility to MI. The relevance of these findings is supported by the vital functions fulfilled by OX40 in mammals as reflected by the high level of evolutionary conservation.     

Study of Association of CD40-CD154 Gene Polymorphisms with Disease Susceptibility and Cardiovascular Risk in Spanish Rheumatoid Arthritis Patients

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Since CD40-CD154 binding has direct consequences on inflammation process initiation, we aimed to replicate previous findings related to disease susceptibility in Spanish RA population. Furthermore, as the major complication in RA disease patients is the development of CV events due to accelerated atherosclerosis, and elevated levels of CD40L/CD154 are present in patients with acute myocardial infarction, we assessed the potential association of CD40 and CD154/CD40L gene variants with CV risk in Spanish RA patients.

Methods

One thousand five hundred and seventy-five patients fulfilling the 1987 ACR classification criteria for RA and 1600 matched controls were genotyped for the CD40 rs1883832, rs4810485 and rs1535045 and CD154 rs3092952 and rs3092920 gene polymorphisms, using predesigned TaqMan single nucleotide polymorphism genotyping assays. Afterwards, we investigated the influence of CD40-CD154 gene variants in the development of CV events. Also, in a subgroup of 273 patients without history of CV events, we assessed the influence of these polymorphisms in the risk of subclinical atherosclerosis determined by carotid ultrasonography.

Results

Nominally significant differences in the allele frequencies for the rs1883832 CD40 gene polymorphism between RA patients and controls were found (p = 0.038). Although we did not observe a significant association of CD40-CD154 gene variants with the development of CV events, an ANCOVA model adjusted for sex, age at the time of the ultrasonography assessment, follow-up time, traditional CV risk factors and anti-cyclic citrullinated peptide antibodies disclosed a significant association (p = 0.0047) between CD40 rs1535045 polymorphism and carotid intima media thickness, a surrogate marker of atherosclerosis.

Conclusion

Data from our pilot study indicate a potential association of rs1883832 CD40 gene polymorphism with susceptibility to RA. Also, the CD40 rs1535045 gene variant may influence development of subclinical atherosclerosis in RA patients.     

Interrelationships between ALOX5AP Polymorphisms,Serum Leukotriene B4 Level and Risk of Acute Coronary Syndrome

Background

We investigated the relationships between the ALOX5AP gene rs10507391 and rs4769874 polymorphisms, serum levels of leukotriene (LT) B4, and risk of acute coronary syndrome (ACS).

Methods

A total of 709 participants, comprising 508 ACS patients (ACS group) and 201 noncoronary artery disease patients with chest pain (control group) were recruited from the Han population of the Changwu region in China. Two polymorphic loci were genotyped using polymerase chain reaction and restriction fragment length polymorphism analysis. Serum LTB4 level was determined by enzyme-linked immunosorbent assay.

Results

Serum LTB4 levels were significantly higher (P<0.001) in the ACS group (median/interquartile range, 470.27/316.32 pg/ml) than in the control group (233.05/226.82 pg/ml). No statistical differences were observed between genotype, allele and haplotype frequencies for the tested loci in either the ACS group or the control group, even after adjustments were made for conventional risk factors by multivariate logistic regression. This suggests there is no association between the ALOX5AP rs10507391 and rs4769874 polymorphisms and ACS risk. Elevated serum LTB4 level was closely linked to ACS risk, and may be independent of traditional risk factors as a risk factor for ACS (P<0.001). There was no significant association between serum LTB4 levels and the two variants in either the ACS group or the control group.

Conclusions

Rs10507391, rs4769874 and its haplotypes in ALOX5AP are unrelated to ACS risk in the Chinese Han population of Changwu, but elevated serum LTB4 level is strongly associated with ACS risk. Serum LTB4 level is not subject to the influence of either the rs10507391, rs4769874 or the haplotype.     

Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases

The interaction between OX40 and OX40 ligand (OX40L) is suggested to provide T cells with an effective costimulatory signals during T cell-APC interaction. To examine the in vivo effect of constitutive OX40/OX40L interaction during immune regulation, we report the establishment of OX40L-transgenic (OX40L-Tg) mice that constitutively express OX40L on T cells. Markedly elevated numbers of effector memory CD4(+) T cells, but not CD8(+) T cells, were observed in the secondary lymphoid organs of OX40L-Tg mice. Upon immunization with keyhole limpet hemocyanin in the absence of adjuvant, profound T cell proliferative responses and cytokine productions were seen in the OX40L-Tg mice as compared with wild-type mice. Furthermore, in OX40L-Tg mice administrated with superantigen, this constitutive OX40/OX40L interaction on CD4(+) T cells completely prevented normal in vivo clonal T cell deletion. Interestingly, OX40L-Tg mice on the C57BL/6 background spontaneously developed interstitial pneumonia and inflammatory bowel disease that was accompanied with a significant production of anti-DNA Ab in the sera. Surprisingly, these diseases were not evident on the OX40L-Tg mice on the BALB/c strain. However, such inflammatory diseases were successfully reproducible in recombination-activating gene (RAG)2-deficient mice upon transfer of OX40L-Tg CD4(+) T cells. Blockade of OX40/OX40L interaction in the recipient RAG2-deficient mice completely prevented disease development. The present results orchestrated in this study indicate that OX40/OX40L interaction may be a vital link in our understanding of T cell-mediated organ-specific autoimmunity.     

中国汉族人群肿瘤坏死因子-α（TNF-α）基因-238G/A和-308G/A多态性与强迫症的关联分析（英文）

目的：探讨在中国汉族人群中强迫症与TNF-a基因-238G/A和-308G/A多态性之间的关联。方法：我们的研究所招募的161例强迫症患者和325名健康对照中,应用PCR-RFLP比较了OCD组和对照组之间的TNF-α基因在-238G/A（rs361525）和-308G/A（rs1800629）位点的基因型和等位基因频率多态性。结果：在中国大陆汉族人群TNF-α基因的OCD组与对照组之间-308 G/A等位基因频率及-238G/A的基因型频率和等位基因频率无显着差异,而-308G/A基因型频率有显著不同。在-308G/A位点,女性强迫症患者和对照组之间的基因型频率关联分析有增高的趋势。结论：我们的研究结果表明,肿瘤坏死因子-α在-308G/A点位多态性可能会影响在中国大陆汉族人群强迫症的发展。     

The association between endothelial lipase ?384A/C gene polymorphism and acute coronary syndrome in a Chinese population

Endothelial lipase (EL) is a novel member of the triglyceride (TG) lipase family. A growing body of evidence has indicated that EL gene polymorphism might contribute to the process of cardiovascular diseases. This study was aimed to reveal the potential relationship between EL -384A/C gene polymorphism and acute coronary syndrome (ACS) in a Chinese Han population. The subjects were composed of 320 ACS patients and 315 age- and gender- matched controls. We detected the EL -384A/C genotypes and allele frequencies by using polymerase chain reaction-restriction fragment length polymorphism analysis. There was significant difference in AA genotype and AC+CC genotype between ACS and control groups (P?=?0.014). The A allele frequency was significantly higher in ACS group than in control group (87.8 vs 83.8?%, P?=?0.041). The relationship between the variant and ACS remained significant after adjusting for current smoker, hypertension, diabetes mellitus, total cholesterol and TG (OR?=?0.682, 95?% CI?=?0.472-0.986). The levels of HDL and ApoA-I were significantly higher in AC+CC genotype than in AA genotype (HDL: 1.20?±?0.35 vs 1.11?±?0.29?mmol/L, P?=?0.001; ApoA-I: 1.14?±?0.25 vs 1.08?±?0.21?g/L, P?=?0.009). We found that the EL -384A/C gene polymorphism might be associated with ACS in Chinese Han population, suggesting that the variant might be involved in the pathogenesis of ACS.     

Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma

Despite the knowledge of many genetic alterations present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating T-cell activation, thereby attenuating anti-tumor responses and increasing cancer susceptibility. Polymorphisms in the CTLA-4 gene are associated with different autoimmune diseases and cancers. The current study evaluated the association of four CTLA-4 gene mutations, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with osteosarcoma in the Chinese population. CTLA-4 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 267 osteosarcoma patients and 282 age-matched healthy controls. Results showed that the CTLA-4 gene +49 AA genotype, +49 A allele, and GTAG haplotype were significantly more frequent in osteosarcoma patients than in controls (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.23-2.95, p?=?0.007; OR 1.32, 95% CI 1.03-1.69, p?=?0.029, and OR?=?1.47, 95% CI 1.03-2.09, p?=?0.033, respectively). The CTLA-4 +49G/A polymorphism and GTAG haplotype are associated with increased risk of osteosarcoma.     

Associations of polymorphisms in the β2-adrenergic receptor gene with essential hypertension in Han Chinese population

The β2-adrenergic receptor (β2-AR) gene has been implicated in the pathogenesis of hypertension. However, the results have been conflicting. In this study, we performed a meta-analysis to assess the associations of 46A/G and 79C/G polymorphisms in β2-AR gene with hypertension risk in Han Chinese population. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, CBM and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95?% confidence interval (CI) was calculated using fixed- or random-effects model. Eleven studies (2,058 cases and 1,459 controls) for 46A/G polymorphism and eight studies (2,219 cases and 1,495 controls) for 79C/G polymorphism were identified. The results suggested that 46A/G polymorphism G allele might increase the risk of hypertension (GG vs. AA: OR?=?1.47, 95?% CI 1.20-1.82). However, no significant association was observed for 79C/G polymorphism (GG vs. CC: OR?=?1.05, 95?% CI 0.61-1.79). The results indicated that 46A/G polymorphism in the β2-AR gene was associated with hypertension susceptibility in Han Chinese population.     

The CD40 gene polymorphism rs1883832 is associated with risk of acute coronary syndrome in a Chinese case-control study

Numerous reports in the past few years have demonstrated that atherosclerosis is a lipid-driven, chronic inflammatory disease of the vessel. Recent studies have indicated that the immune mediator CD40-CD40L (CD40 ligand), which is expressed on several inflammatory cells within human atherosclerotic lesions, has roles in atherogenesis. A functional polymorphism (-1C>T, rs1883832) in the 5' untranslated region of TNFRSF5 gene has been reported to affect CD40 expression and be associated with several chronic inflammatory and autoimmune diseases. The aim of the present study was to validate the potential coronary artery disease susceptibility marker in a Chinese case-control study. A total of 160 patients with acute coronary syndrome (ACS) and 180 control subjects were used to genotype and identify this single-nucleotide polymorphism by polymerase chain reaction-restriction fragment length polymorphism and sequencing, respectively. Peripheral blood mononuclear cells were isolated and incubated with interferon-γ with or without pretreatment of fluvastatin, followed by measurement of CD40 expression using flow cytometry. In addition, soluble CD40L was determined by ELISA as another biomarker of coronary artery disease. The distribution of the rs1883832 genotypes (CC, CT, and TT) was 33.1%, 54.4%, and 12.5% in the ACS group and 22.8%, 53.3%, and 23.9% in controls, respectively. The frequency of the C allele was significantly higher among ACS patients compared with controls (60.3% vs. 49.4%, odds ratio=1.554, 95% confidence intervals: 1.146-2.107, p<0.05). ACS patients showed a significant increase of CD40 and sCD40L coexpression compared with controls (p<0.05). Cell culture experiments showed that CC carriers presented significantly higher CD40 expression levels than CT and TT subjects (p<0.05). Additionally, fluvastatin suppressed CD40 expression in all three genotypes. These data suggest that the single-nucleotide polymorphism of CD40 gene is associated with susceptibility to ACS in Chinese population, and the polymorphism may influence the CD40 production. These expand the understanding of inflammatory mechanisms during atherogenesis.     

Association of inflammatory chemokine gene CCL2I/D with bladder cancer risk in North Indian population

Chemokine genes have been proposed as good candidate genes for conferring susceptibility to Bladder cancer (BC). We examined the combined effect of multiple alleles of pro inflammatory chemokine genes for determining the risk of BC. We tested association of three gene polymorphisms of CCL2I/D (rs3917887), CCL2A2518G (rs1024611) and CCR2V64I (rs1799864) with BC risk in North Indian population. Genotypes were assessed in hospital-based case-control study comprising of 200?BC patients and 200 healthy controls. Genomic DNA was isolated from blood and genotyping done using PCR-RFLP method. In CCL2I/D polymorphism, the heterozygous genotype (I/D) showed high risk of BC p?相似文献   

The SNP rs1883832 in CD40 Gene and Risk of Atherosclerosis in Chinese Population: A Meta-Analysis

Background

The complications of atherosclerosis such as coronary and cerebrovascular disease, are the most prevalent causes of mortality and morbidity worldwide. A single nucleotide polymorphism (SNP) rs1883832 (-1C/T) in CD40 gene has been recently suggested to contribute to the susceptibility to atherosclerosis in Chinese population; however, previous genetic association studies yielded inconsistent results.

Methods

A meta-analysis of eligible studies reporting the association between rs1883832 and atherosclerosis in Chinese population was carried out.

Results

Pooling 7 eligible case-control studies involving 2129 patients and 1895 controls demonstrated a significant association between rs1883832 and atherosclerosis under dominant model [odds ratio (OR) = 1.631, 95% confidence interval [CI] [1.176, 2.260] in Chinese population with evident heterogeneity. Meta-regression analysis indicated that the heterogeneity could be completely explained by disease category. In subgroup analysis, rs1883832 conferred ORs of 2.866 (C/C versus T/T, 95%CI [2.203, 3.729]) and 1.680 (C/T versus T/T, 95%CI [1.352, 2.086]) for coronary artery disease (CAD) under co-dominant model without heterogeneity. Similar results were obtained for acute coronary syndrome (ACS) (C/C versus T/T, 3.674, 95%CI [2.638, 5.116]; C/T versus T/T, 1.981, 95%CI [1.483, 2.646]). The other genetic models including dominant, recessive and additive models, yielded consistent results without heterogeneity for CAD and ACS, respectively. However, a protective role was found for C allele in ischemic stroke (IS) under recessive model (0.582, 95%CI [0.393, 0.864]) and additive model (0.785, 95%CI [0.679, 0.909]) with reduced heterogeneity.

Conclusions

This meta-analysis provided evidence of association of rs1883832 C allele with an overall increased risk of atherosclerosis but distinct effect of C allele on CAD (including ACS) and IS in Chinese population, respectively.     

Association of deoxyribonuclease I genetic polymorphisms with myocardial infarction in Han Chinese

Deoxyribonuclease I gene exhibits polymorphisms, including a single nucleotide polymorphism (A2317G) and a 56 bp variable number of tandem repeat, designated as HumDN1. G2317 was regarded as an independent risk factor for Japanese myocardial infarction (MI) patients. We investigated the association between either A2317G or HumDN1 polymorphism of deoxyribonuclease I gene and MI in Han Chinese population. A2317G and HumDN1 polymorphisms in 278 MI patients and 297 unrelated controls were detected by PCR and PCR-restriction fragment length polymorphism. Plasma lipids were measured in fasting state by biochemical methods. A new HumDN1 genotype -HumDN1 4/6 was found in Han Chinese MI patients. Genotype distributions and allele frequencies of A2317G and HumDN1 did not differ between MI patients and control group (all P > 0.05). In addition, none of estimated haplotypes significantly increased or decreased the risk of MI. In analysis of covariance, plasma total cholesterol was observed to be associated with HumDN1 genotypes in MI patients (P = 0.02). Our data suggest HumDN1 genotypes are related to total cholesterol levels in Han Chinese MI patients, but deoxyribonuclease I gene polymorphisms are not associated with susceptibility to MI in Han Chinese.     

Negative regulation of IL-17 production by OX40/OX40L interaction

The T-cell cytokine IL-17 is implicated in multiple inflammatory diseases through its induction of several pro-inflammatory cytokines and chemokines in a broad range of cell targets. Production of IL-17 defines the Th17 subset of helper T-cells associated with protection against microorganisms, a profile best characterized in the murine system. Multiple regulators of Th17 cell differentiation and IL-17 production are reported, but the impact of OX40L is not described. OX40 ligand (OX40L) is an early-stage activator of T-cells through its interaction with CD134 (OX40) that is up-regulated on antigen challenged T-cells. Here, we show that OX40L suppresses IL-17 production by PHA-stimulated human PBMC and purified CD4 and CD8 cells. In agreement with prior reports, OX40L signaling through CD134 increased IFNgamma and IL-4, both of which are reported to inhibit the production of IL-17. OX40L suppression of IL-17 was completely reversed by a neutralizing IFNgamma antibody while there was no effect with a neutralizing IL-4 antibody. Moreover, OX40L also suppressed IL-17 in the presence of IL-23, an established inducer of IL-17 and differentiation factor for Th17 cells. Presuming mediation by IFNgamma, we evaluated expression of this cytokine in the presence of OX40L and IL-23. Surprisingly, IL-23 also induced IFNgamma by PHA-stimulated T-cells and this effect was enhanced in the presence of OX40L. Addition of the IFNgamma antibody not only reversed the OX40L suppression of IL-17 in the presence of IL-23, it markedly enhanced the level of IL-17. These results further establish IFNgamma as a primary modulator of IL-17 production in the human cells, much as in the murine system.     

Genetic polymorphisms in MMP 2, 3 and 9 genes and the susceptibility of osteosarcoma in a Chinese Han population

Background: There are no data about the role of MMPs polymorphism in development of osteosarcoma.

Patients and methods: Two-hundred fifty-one patients with osteosarcoma and 251 healthy controls were included to investigate the association between the MMP2, 3, 9 polymorphisms and the risk of osteosarcoma.

Results: Compared with the MMP2 SNP rs243865 homozygote CC, The heterozygous CT genotype was associated with significantly increased risk for osteosarcoma (OR?=?1.86, 95% CI?=?1.18–4.22, p?=?0.014); the TT genotype was associated with increased risk for osteosarcoma (OR?=?1.92, 95% CI?=?1.21–3.52, p?=?0.028). However, the genotype and allele frequencies of MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were not significantly different.

Conclusion: MMP2 rs243865 genotype was associated with increased risk for development of osteosarcoma in Chinese Han population.     

A tagging SNP in <Emphasis Type="Italic">ALOX5AP</Emphasis> and risk of stroke: a haplotype-based analysis among eastern Chinese Han population

A genome-wide approach found significant association of two at-risk haplotypes (HapA, HapB) in the ALOX5AP gene with myocardial infarction and stroke. To date, it is still controversial whether ALOX5AP gene polymorphisms are risk factors for stroke. The aim of the present study is to investigate the association between the ALOX5AP gene polymorphism and the risk for stroke in Eastern Chinese Han population with a haplotype-based analysis. We conducted a comprehensive association study of 507 stroke patients and 510 healthy controls to assess the association between the ALOX5AP tagging single-nucleotide polymorphisms (tSNPs) and stroke risk. Genotyping was performed using the PCR–RFLP assay. In the single-locus analysis, we found that the rs9579646 AG genotype was associated with a marginally decreased risk for stroke (adjusted odds ratio, 0.65; 95% confidence interval, 0.45–0.96), compared with the AA genotype. Haplotype-based association analysis of block 2 involving rs10507391 and rs12429692 revealed that the decreased risk of stroke was significantly associated with haplotype AA (OR, 0.66; 95% CI, 0.46–0.95). These results suggested that the genetic variants in ALOX5AP might modulate the risk of stroke in Eastern Chinese Han population. The frequencies of single-marker alleles and haplotypes showed remarkable differences from those in other populations.     

Association of PTEN polymorphisms with susceptibility to hepatocellular carcinoma in a Han Chinese population

The phosphate and tension homolog (PTEN) is a tumor suppressor gene that controls a variety of biological processes including cell proliferation, migration, and death. The association of PTEN polymorphisms with risk for many cancers has been reported, but hepatocellular carcinoma (HCC) has not yet been studied. The present study is the first attempt to assess the association of PTEN polymorphisms with HCC susceptibility. We genotyped one insertion/deletion polymorphism (rs34421660) by polymerase chain reaction (PCR) method and three tag single-nucleotide polymorphisms (rs10490920, rs532678, and rs701848) by polymerase chain reaction-restriction fragment length polymorphism in 134 HCC patients and 215 healthy controls. We found that the four polymorphisms were not associated with HCC, at both the allele and genotype levels. However, after reconstructing PTEN haplotypes according to genotyping data and linkage disequilibrium status of four polymorphisms, we found that the T-C-C-del haplotype was associated with decreased HCC risk (odds ratio?=?0.19, 95% confidence interval?=?0.06-0.56) and the T-T-T-ins haplotype was associated with increased HCC risk (odds ratio?=?1.63, 95% confidence interval?=?1.14-2.33). Thus, our results prove that PTEN haplotypes may be associated with HCC susceptibility in a Chinese Han population.     

Lysyl oxidase polymorphisms and ischemic stroke—a case control study

Ischemic stroke is a common neurological disease and causes severe disability and death worldwide. Lysyl oxidase (LOX) plays a crucial role in the maintenance of extracellular matrix stability and may participate in vascular remodeling in the development of ischemic stroke. The objective of this study is to identify polymorphisms in LOX genes and investigate the association between LOX polymorphisms and the susceptibility to ischemic stroke in the Chinese population. Genomic DNA sequencing analysis was performed on all 7 exons and all exon/intron splice sites of lysyl oxidase and 850?bp upstream, including the predicted promoter region in 25 control subjects. The identified polymorphisms were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 702 ischemic stroke cases and 733 age-matched controls. Data were analyzed using the Chi-square test. Two polymorphisms in the LOX gene, 473G/A (rs1800449) and rs2278226, were observed in the Chinese population. Frequencies of LOX 473AA genotype and A allele were significantly higher in ischemic stroke patients than in controls (odds ration (OR)?=?1.76, 95?% confidence interval (CI) 1.16-2.67, P?=?0.007; and OR?=?1.33, 95?% CI 1.10-1.60, P?=?0.003). Also, the prevalence of AC haplotype was significantly increased in ischemic stroke cases (OR?=?1.32, 95?% CI 1.10-1.60, P?=?0.004). Our data suggest that the G473A polymorphism of LOX gene could be a new risk factor for ischemic stroke.