Association between Ser311Cys polymorphism in the dopamine D2 receptor gene and schizophrenia risk: a meta-analysis in Asian populations

Numerous studies have evaluated the association between Ser311Cys (rs1801028, C>G) polymorphism of the dopamine D2 receptor (DRD2) gene and schizophrenia risk. However, the specific association is still controversial. We examined whether DRD2 Ser311Cys polymorphism confers schizophrenia risk in Asian populations. Sixteen studies were retrieved reporting on a total of 2268 schizophrenia patients and 2423 healthy controls. Meta-analysis of the results showed significant associations between Ser311Cys polymorphism and schizophrenia risk in the comparisons of G versus C (odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.18-1.83, P = 0.0006) and CG+GG versus CC (OR = 1.45, 95%CI = 1.16- 1.82, P = 0.001). In a subgroup analysis by nationality, we found a significant association between Ser311Cys polymorphism and schizophrenia risk in the comparisons of G versus C and CG+GG versus CC genotype in the Japanese population (OR = 1.75, 95%CI = 1.30-2.35, P = 0.0002; OR = 1.72, 95%CI = 1.27-2.33, P = 0.0004; respectively) but not in Chinese and Indian populations. In conclusion, the G allele of DRD2 Ser311Cys polymorphism involves a potential risk factor for schizophrenia in Asian populations, especially in the Japanese population.     

Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans

Catechol-O-methyltransferase (COMT) inactivates circulating catechol hormones, catechol neurotransmitters, and xenobiotic catecholamines by methylating their catechol moieties. The COMT gene has been suggested as a candidate gene for schizophrenia through linkage analyses and molecular studies of velo-cardio-facial syndrome. A coding polymorphism of the COMT gene at codon 108/158 (soluble/membrane-bound form) causing a valine to methionine substitution has been shown to influence enzyme activity, but its association with schizophrenia is inconclusive. We have screened 17 known polymorphisms of the COMT gene in 320 Korean schizophrenic patients and 379 controls to determine whether there is a positive association with a nonsynonymous single-nucleotide polymorphism (rs6267) at codon 22/72 (soluble/membrane-bound form) causing an alanine-to-serine (Ala/Ser) substitution. With the Ala/Ala genotype as a reference group, the combined genotype (Ala/Ser and Ser/Ser)-specific adjusted odds ratio was 1.82 (95% CI=1.19–2.76; P=0.005), suggesting the Ser allele as a risk allele for schizophrenia. However, the Val/Met polymorphism was not associated with an increased risk of schizophrenia in Koreans (OR=0.88, 95% CI=0.64–1.21; P=0.43). The Ala72Ser substitution was correlated with reduced COMT enzyme activity. Our results support previous reports that the COMT haplotype implicated in schizophrenia is associated with low COMT expression.     

PPARGC1A基因Thr394Thr/Gly482Ser多态性与2型糖尿病的关联研究

对344例2型糖尿病患者和307名正常人的PPARGC1A基因单核苷酸多态性rs2970847(Thr394Thr)和rs8192678(Gly482Ser)与2型糖尿病的关系进行了单标记和单体型关联分析以及Logistic回归分析。在单标记分析中,对照组与病例组Thr394Thr的基因型和等位基因频率有显著差异(基因型, P =0.006; 等位基因, P < 0.001); Logistic回归和单体型分析表明, Thr394Thr的AA基因型及Thr394(ACA)-Ser482单体型增加患2型糖尿病的风险。Gly482Ser的基因型和等位基因频率在对照组与病例组间无显著差异。PPARGC1A基因是湖北汉人的一个2型糖尿病易感基因。     

Fibroblast growth factor receptor 4 polymorphisms and coronary artery disease: a case control study

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in vascular system. FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to coronary artery disease (CAD) in the Chinese population. We identified three polymorphisms in the FGFR4 gene, rs351855G/A (Gly388Arg), rs145302848C/G and rs147603016G/A, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 658 CAD cases and 692 healthy controls. Results showed that frequencies of GA genotype, AA genotype and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls [odds ratio (OR) = 0.79, 95 % confidence intervals (CI) 0.62-0.99, P = 0.042; OR = 0.58, 95 % CI 0.41-0.81, P = 0.002; and OR = 0.77, 95 % CI 0.66-0.90, P = 0.001, respectively]. The rs147603016GA genotype and A allele also showed lower numbers in CAD cases (OR = 0.58, 95 % CI 0.36-0.93, P = 0.025; and OR = 0.59, 95 % CI 0.40-0.95, P = 0.028). The rs145302848C/G polymorphism did not show any correlation with CAD. Haplotype analysis revealed that the prevalence of ACG haplotype (rs351855, rs145302848 and rs147603016) was significantly decreased in CAD patients (P = 0.002). Our data suggested that the FGFR4 rs351855G/A (Gly388Arg) and rs147603016G/A polymorphisms could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases.     

Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

Background

Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants.

Objective

To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients.

Methods

303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA).

Findings and conclusions

In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, –521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the –521 C/T (rs1800955) polymorphism in the promoter.     

Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia

Haploinsufficiency of 22q11 genes including catechol- O -methyltransferase (COMT) and proline dehydrogenase (PRODH) may result in structural and functional brain abnormalities and increased vulnerability to schizophrenia as observed in patients with microdeletions of 22q11. Thus, COMT and PRODH could be modifier genes for schizophrenia. We examined association of polymorphisms in COMT and PRODH with brain anatomy in young patients with schizophrenia and schizoaffective disorder. We acquired structural magnetic resonance imaging data from 51 male patients and genotyped two single nucleotide polymorphisms (SNPs) in the COMT gene and three in the PRODH gene. Statistical Parametric Mapping software and optimized voxel-based morphometry were used to determine regional gray matter (GM) and white matter (WM) density differences, and total GM and WM volume differences between genotype groups. Two nonsynonymous SNPs in the PRODH gene were associated with bilateral frontal WM density reductions and an SNP in the P2 promoter region of COMT (rs2097603) was associated with GM increase in the right superior temporal gyrus. Furthermore, we found evidence for COMT and PRODH epistasis: in patients with a COMT Val allele (rs4680) and with one or two mutated PRODH alleles, we observed increased WM density in the left inferior frontal lobe. Our results suggest that genetic variation in COMT and PRODH has significant effects on brain regions known to be affected in schizophrenia. Further research is needed to investigate the role of 22q11 genes on brain structure and function and their role in vulnerability for schizophrenia.     

Fibroblast growth factor receptor 4 polymorphisms and susceptibility to coronary artery disease

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play crucial roles in vascular smooth muscle cell proliferation and atherosclerosis and, therefore, may potentially affect the development of coronary artery disease (CAD). FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to CAD in the Chinese population. Two polymorphisms, rs351855 (Gly388Arg) and rs641101, were detected by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing in 687 CAD cases and 732 age-matched controls. Data were analyzed using the chi-square test. Results showed that frequencies of GA genotype, AA genotype, and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls (odds ratio (OR)=0.78, 95% confidence intervals (CIs): 0.62-0.98, p=0.034; OR=0.58, 95% CI: 0.42-0.80, p=0.001; and OR=0.77, 95% CI: 0.66-0.90, p=0.001, respectively). The rs641101 polymorphism did not show any correlation with CAD. Haplotype analysis revealed that rs351855 and rs641101 AG haplotype also had lower frequency in CAD patients (OR=0.79, 95% CI: 0.67-0.92, p=0.002). Our data suggested that the FGFR4 rs351855 (Gly388Arg) polymorphism and AG haplotype (rs351855 and rs641101) could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases.     

Polymorphisms of CYP1B1 and COMT in breast and endometrial cancer

CYP1B1 and COMT code for the key enzymes of catecholestrogen biosynthesis and metabolism, and their polymorphisms determine a variation of enzymic activities. RFLP analysis was used to study the allele and genotype frequency distributions of CYP1B1 polymorphisms Arg48Gly, Ala119Ser, and Val432Leu and COMT polymorphism Val158Met in 210 breast cancer patients, 138 endometrial cancer patients, and 152 healthy women. The COMT polymorphism showed no significant association with breast or endometrial cancer. For the first time, such association was observed for the CYP1B1 polymorphisms. CYP1B1 allele C (Arg48), which codes for the enzyme more active in estradiol 4-hydroxylation, was associated with higher risk of breast (OR = 3.22, CI 2.34-4.43, p = 0.000) and endometrial (OR = 2.43, CI 1.72-3.44, p = 0.000) cancer. Similar data were obtained for CYP1B1 allele G (Ala119): OR = 2.18, CI 1.58-3.01, p = 0.000 in breast cancer and OR = 2.52, CI 1.78-3.56, p = 0.000 in endometrial cancer. Risk of endometrial, but not breast, cancer was significantly higher in carriers of CYP1B1 genotype Val432/Val. This was explained by stronger estrogen dependence and, consequently, higher estrogen reactivity of the endometrium as compared with the mammary gland.     

Association between peroxisome proliferator-activated receptor gamma coactivator-1 alpha polymorphism and hypertension in Mongolians in Inner Mongolia

We investigated a possible association of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) Gly482Ser polymorphism with hypertension in Mongolians in Inner Mongolia. A total of 787 subjects were enrolled randomly, including 390 hypertension patients and 397 healthy controls. Triglycerides, cholesterol, and fasting plasma glucose were measured, and body mass index was calculated. PCR-RFLP was used to analyze Gly482Ser polymorphisms. There were significant differences in triglycerides, fasting plasma glucose, and body mass index between hypertension patients and healthy controls. Cholesterol levels did not differ significantly. The PGC-1α gene GG, GA and AA genotype distributions were 37.2, 48.5 and 14.4%, respectively, in patients and 48.6, 37.3 and 14.1% in healthy controls. The frequencies of PGC-1α genotype GA and allele A were significantly different between hypertension patients and healthy Mongolians. We concluded that PGC-1α Gly482Ser polymorphism is associated with hypertension in Mongolians in Inner Mongolia.     

Association between promoter variants of interleukin-18 and schizophrenia in a Han Chinese population

An increasing amount of evidence suggests that interleukin-18 (IL-18) plays a pivotal role in the pathophysiology of schizophrenia. However, association between single nucleotide polymorphism of IL-18 and the risk of schizophrenia has not been clarified. This study examined whether two promoter polymorphisms -137 G/C (rs187238) and -607 C/A (rs1946518) of IL-18 were associated with schizophrenia and six clinical symptoms (disorder of perception, thought disorder, disturbance of emotion, disorder of behavior and volition, suicide action, and aggressive action) to provide data for screening high-risk Han Chinese individuals. Three hundred seventy-two schizophrenic patients and 353 healthy controls from a Han Chinese population were examined to assess their genotype and allele frequencies of the two promoter polymorphisms of IL-18. The genotype distributions in both patients and controls were within Hardy-Weinberg equilibrium. No significant differences were observed in the genotype or the allele frequencies of the two single-nucleotide polymorphisms between patients and controls. However, genotype frequencies of -607 C/A showed significant differences between patients and controls in the appearance of perception disorder (χ2 = 6.153, p = 0.046). A significant difference was detected in -137 G/C between patients and controls in the appearance of aggressive action (χ2 = 3.909, p = 0.048). In conclusion, IL-18 gene promoter polymorphisms may not contribute to the susceptibility of schizophrenia in a Han Chinese population, but two single-nucleotide polymorphisms, -137 G/C and -607 C/A, may play a role in the development of perception disorder and aggressive action, respectively.     

DDAH2启动子区-1150C/A多态性与中国汉族人群冠心病的遗传易感性研究

目的:研究DDAH2启动子区-1150 C/A rs805304多态性与中国汉族人群冠心病之间的相关性。方法:应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)的分析方法,对381例冠心病患者和629例健康人群中DDAH2基因A-1150C rs805304多态进行基因分型。结果:病例组和对照组A-1150C rs805304位点基因型分布均符合Hardy-Wenberg平衡;两组间A-1150C位点基因型间无显著性的差异(P=0.34);病例组和对照组A-1150C位点的等位频率分布也无显著的差别,但是在冠心病病例中,A等位频率有低于C等位频率的趋势(P=0.069)。结论:DDAH2启动子区-1150 C/A rs805304多态性与中国汉族人群冠心病的发病不相关。     

Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese population

Several lines of evidence suggest that metabolic changes in the kynurenic acid (KYNA) pathway are related to the etiology of schizophrenia. The inhibitor of kynurenine 3-monooxygenase (KMO) is known to increase KYNA levels, and the KMO gene is located in the chromosome region associated with schizophrenia, 1q42-q44. Single-marker and haplotype analyses for 6-tag single nucleotide polymorphisms (SNPs) of KMO were performed (cases = 465, controls = 440). Significant association of rs2275163 with schizophrenia was observed by single-marker comparisons (P = 0.032) and haplotype analysis including this SNP (P = 0.0049). Significant association of rs2275163 and haplotype was not replicated using a second, independent set of samples (cases = 480, controls = 448) (P = 0.706 and P = 0.689, respectively). These results suggest that the KMO is unlikely to be related to the development of schizophrenia in Japanese.     

Evidence for statistical epistasis between catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase (COMT) and polymorphisms in RGS4, G72 (DAOA), GRM3, and DISC1: influence on risk of schizophrenia

Catechol-O-methyltransferase (COMT) regulates dopamine degradation and is located in a genomic region that is deleted in a syndrome associated with psychosis, making it a promising candidate gene for schizophrenia. COMT also has been shown to influence prefrontal cortex processing efficiency. Prefrontal processing dysfunction is a common finding in schizophrenia, and a background of inefficient processing may modulate the effect of other candidate genes. Using the NIMH sibling study (SS), a non-independent case-control set, and an independent German (G) case-control set, we performed conditional/unconditional logistic regression to test for epistasis between SNPs in COMT (rs2097603, Val158Met (rs4680), rs165599) and polymorphisms in other schizophrenia susceptibility genes. Evidence for interaction was evaluated using a likelihood ratio test (LRT) between nested models. SNPs in RGS4, G72, GRM3, and DISC1 showed evidence for significant statistical epistasis with COMT. A striking result was found in RGS4: three of five SNPs showed a significant increase in risk [LRT P-values: 90387 = 0.05 (SS); SNP4 = 0.02 (SS), 0.02 (G); SNP18 = 0.04 (SS), 0.008 (G)] in interaction with COMT; main effects for RGS4 SNPs were null. Significant results for SNP4 and SNP18 were also found in the German study. We were able to detect statistical interaction between COMT and polymorphisms in candidate genes for schizophrenia, many of which had no significant main effect. In addition, we were able to replicate other studies, including allelic directionality. The use of epistatic models may improve replication of psychiatric candidate gene studies.     

Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia

Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.     

Association of IFN‐γ polymorphisms with ankylosing spondylitis risk

The case‐control study was designed to investigate the genetic effects of interferon‐gamma (IFN‐γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN‐γ polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Hardy‐Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi‐square test to evaluate the association between AS susceptibility and IFN‐γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563‐22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286‐1.704, P  = 0 .003). While the genotype and allele frequencies of IFN‐γ rs1861494 polymorphism were not significantly different between patients and controls (P  > 0.05 for all), IFN‐γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population.     

Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis in a Han Chinese population

The aim of this study was to perform an association study between two single nucleotide polymorphisms (SNPs) rs2910164 G>C and rs3746444 T>C in pre-miRNA (hsa-mir-146a and hsa-mir-499) and rheumatoid arthritis (RA) in the Han Chinese population. 208 Han Chinese patients with RA and 240 healthy controls were recruited in this study. The SNPs was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Anti-cyclic citrullinated peptide (anti-CCP) antibody was measured by enzyme linked immunosorbent assay and rheumatoid factor (RF) was measured by rate nephelometry. The genotype frequencies between cases and controls were compared by χ(2) analysis. No significant association between the SNPs (rs2910164 and rs3746444) and RA was observed (P = 0.631 and 0.775, respectively), and the SNPs did not show any association with the RF-positive (P = 0.631 and 0.775, respectively). However, there was a significant difference on the level of anti-CCP antibody between different genotypes in rs3746444 (P = 0.007). The heterozygote CT had significantly higher level of anti-CCP antibody compared with homozygote CC and TT (P = 0.054 and 0.003, respectively). We first investigated the association between the SNPs (rs2910164 G>C and rs3746444 T>C) in the pre-miRNA (hsa-mir-146a and hsa-mir-499) and RA in a Han Chinese population. We did not find a significant association between the SNPs and the susceptibility to RA, while the SNP rs3746444 may affect anti-CCP antibody production.     

Association of genetic polymorphisms in vitamin D receptor gene and susceptibility to sporadic prostate cancer

Genetic and environmental factors are involved in prostate cancer (PCa) etiology. Single nucleotide polymorphisms (SNPs) may contribute to the PCa pathogenesis. The goal of this study is to determine the role of vitamin D receptor (VDR) gene polymorphisms and haplotypes in the development and progression of sporadic PCa. One hundred and thirty-three PCa patients and 157 age-matched healthy controls were genotyped for the Apa I (rs7975232), Bsm I (rs1544410) and Taq I (rs731236) polymorphisms in VDR gene by using polymerase chain reaction-restriction fragment length polymorphism. An association was observed between the Apa I polymorphism and PCa predisposition (P = 0.03). When compared with AA genotype, there was a highly notable difference in the frequencies of the Aa (P = 0.02), aa (P = 0.026) and Apa I 'a' allele carriers (Aa + aa) (P = 0.009) genotypes. Furthermore, we found a statistical difference in the allele frequencies of the Apa I polymorphism between the sporadic PCa patients and control subjects (P = 0.013). The genotype distribution for the Bsm I and Taq I polymorphisms were similar between cases and controls (P > 0.05). No clinically significant relationship was found between the three-locus haplotypes and development of sporadic PCa. The genotype frequencies for the three polymorphisms of the VDR gene within subgroups of PCa (defined by tumor stage, Gleason score, PSA levels) were also analyzed, but no statistically noteworthy difference was observed (P > 0.05). As far as we know, this is the first study which investigates the relationship between VDR genotypes and sporadic PCa in the Turkish population. Our findings suggest that the VDR ApaI (rs7975232) polymorphism may play a role in the development of sporadic PCa.     

Toll-like receptor polymorphisms and vasculitis susceptibility: meta-analysis and systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confers susceptibility to vasculitis. A literature search was conducted using the PubMed and Embase. A meta-analysis on the associations between the TLR4 Asp299Gly polymorphisms and vasculitis was carried out using allele contrast, dominant, and codominant models and a systematic review of other TLR polymorphisms. Fourteen studies involving 2,064 patients and 2,481 controls were included in this systematic review, which comprised nine on Behcet’s disease (BD), three on giant cell arteritis (GCA), and one on Henoch–Schenlein purpura (HSP). Meta-analysis of six studies showed a significant association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis and GCA (Odds ratio [OR] = 1.368, 95 % confidence interval [CI] = 1.300–1.815, p = 0.030; OR = 1.523, 95 % CI = 1.099–2.112, p = 0.012). Under a random effects model, the adjusted ORs calculated using the trim and fill technique revealed an association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis (OR = 1.544, 95 % CI = 1.091–2.185, p < 0.05). Stratification by vasculitis type using the codominant model showed the trend for the association with GCA (OR = 1.569, 95 % CI = 0.970–2.538, p = 0.066). There were three studies on the TLR2 Arg753Gln polymorphism and two on the TLR4 Thr399Ile polymorphism; no association with vasculitis was evident. Among the TLR2, TLR7, and TLR9 polymorphisms included in this review, one Asian study revealed a significant association between the TLR7 rs5743733 and rs3853839 with BD (p = 0.002, 0.036) and one Asian study showed an association of TLR9 rs352140 with BD (p = 0.009). This meta-analysis demonstrates that the TLR4 Asp299Gly polymorphism may confer susceptibility to GCA. The review of published data suggests that other TLR polymorphisms such as TLR7 and TLR9 may play a role in vasculitis.