Genetic association between the dopamine D3 gene polymorphism (Ser9Gly) and schizophrenia in Japanese populations: evidence from a case-control study and meta-analysis

Dysregulation in the dopaminergic system has been implicated in the pathophysiology of schizophrenia (SCZ). Dopamine D3 receptors (DRD3) concentrated in limbic regions of the brain (important for cognitive, emotional and endocrine function) may be particularly relevant to SCZ. A recent meta-analysis with mixed ethnicities reported a marginal significant association between the Ser9Gly homozygosity in the first exon of the DRD3 gene and SCZ. To further evaluate the controversial association between this polymorphism and SCZ, a case–control study and meta-analysis was conducted using the homogeneous Japanese population. In our Japanese case–control sample (246 cases/198 controls), we found an association between the DRD3 Ser9Gly polymorphism and SCZ (genotype: χ² = 9.76, d.f. = 2, p = 0.008; Ser allele versus Gly allele: χ² = 7.96, d.f. = 1, p = 0.0048; OR = 0.65; 95% CI = 0.48–0.88). However in a meta-analysis of nine Japanese case–control studies comprising 2056 subjects the association between DRD3 Ser9Gly polymorphism and SCZ did not persisted. The Mantel–Haenszel pooled OR for SCZ among carriers of the DRD3 Ser9Gly homozygosity (Ser/Ser homozygotes and Gly/Gly homozygotes) of the nine Japanese studies was 1.16 (95% CI 0.97–1.39), pointing to a non-significant effect of the DRD3 Ser9Gly homozygosity as a risk factor for SCZ. Overall, our results suggest that the DRD3 Ser9Gly polymorphism may not confer susceptibility to SCZ in the Japanese population. Given that the Ser9Gly variant may play a putative role in DRD3 function, further studies on the DRD3 with linked variants are warranted.     

Gene–gene interaction analysis of personality traits in a Japanese population using an electrochemical DNA array chip analysis

It has been suggested that genes involved in the central dopaminergic pathway may contribute to personality traits. However, the results of association studies for these genes have not been consistent. The present study investigated the relationship between the specific polymorphisms of MAO-A, COMT, DRD2, DRD3 and personality traits in Japanese women using a novel genotyping method involving electrochemical DNA array (ECA) chip analysis. Single marker association analysis for each mutation revealed no significant association between scores for Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) items. Gene–gene interaction analysis showed that a MAO-A 30-bp repeat × COMT (Val158Met) × DRD3 (Ser9Gly) had a marginally significant association with Agreeableness (P = 0.0547). The present results suggest that a combination of polymorphisms of MAO-A, COMT, and DRD3 might affect personality traits in Japanese women.     

A cluster of single nucleotide polymorphisms in the 5'-leader of the human dopamine D3 receptor gene (DRD3) and its relationship to schizophrenia

The association between schizophrenia and the Ser9Gly variant of the dopamine D3 receptor gene (DRD3) has been the subject of numerous studies. Under meta-analysis this site, or one or more in linkage disequilibrium with it, appears to contribute a small increase to the relative risk of schizophrenia. In this study, 768 bp of the 5'-leader region of DRD3 mRNA was screened for polymorphisms to assess their contribution to the association of DRD3 with schizophrenia. A cluster of three single nucleotide polymorphisms (SNPs) was identified in tight linkage disequilibrium with each other and with the Ser9Gly polymorphism. One of the 5'-leader SNPs encodes a Lys9Glu variant within a 36 amino acid residue stretch of an upstream open reading frame (uORF). Two common haplotypes are found in the population examined; one is linked to the Ser9 coding variant and the other to the Gly9 variant. A panel of 73 schizophrenic patients and 56 matched controls recruited from the East Anglia region of the United Kingdom was screened for disease association at these sites. Since the 5'-leader and coding sites are in tight disequilibrium, the combined genotype of all 4 sites was scored for each patient. A significant association was seen between disease and the frequency distribution of these genotypes (chi2 = 13.19, d.f. = 3, P = 0.0042; Cochran method for sparse cells applied). A 20% excess of one of the heterozygous genotypes, in which the sequences differ at three of the four SNPs, including Ser9/Gly9 in the receptor and Lys9/Glu9 in the uORF, was found in the patient group. An absence of association of disease with the Ser9Gly polymorphism had previously been reported for this panel. This suggests that these SNPs and the corresponding coding changes may exert a combined or synergistic effect on susceptibility to schizophrenia.     

Association between functional Fc receptor-like 3 (FCRL3) −169 C/T polymorphism and susceptibility to seropositive rheumatoid arthritis in Asians: A meta-analysis

Objective

The aim of this study was to determine whether the functional Fc receptor like-3 (FCRL3) −169 C/T polymorphism confers susceptibility to rheumatoid arthritis (RA).

Methods

A meta-analysis was conducted on the associations between the FCRL3 −169 C/T polymorphism and RA.

Results

A total of 17 comparison studies including 11,170 patients and 11,142 controls were considered in the meta-analysis. The meta-analysis showed no association between RA and the FCRL3 −169 C allele in study subjects (OR = 1.046, 95% CI = 0.997–1.098, p = 0.068). Stratification by ethnicity indicated an association between the FCRL3 −169 C allele and RA in Asians (OR = 1.101, 95% CI = 1.035–1.174, p = 0.002), but not in Europeans. Stratification of patients according to the presence of rheumatoid factor (RF) revealed a different significant association between the C allele and RA in RF-positive and RF-negative RA patients. Stratification by ethnicity indicated an association between the FCRL3 −169 C allele and RF-positive RA in Asians (OR = 1.093, 95% CI = 1.004–1.189, p = 0.040), but not in Europeans.

Conclusions

This meta-analysis demonstrates that the FCRL3 −169 C/T polymorphism may confer susceptibility to seropositive RA in Asians.     

Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia

Dopamine D3 receptor (DRD3) was demonstrated to have important implications in schizophrenia, because it binds antipsychotic drugs and is abundant in the limbic system of the brain. Several groups attempted to find an association between a serine-to-glycine polymorphism at codon 9 of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. We conducted a case-control association study in Han Chinese schizophrenic patients from Taiwan, to examine the relationship of this serine-to-glycine polymorphism and schizophrenia. We noted no significant differences of genotype distribution, allele frequencies, or homozygosity proportion of this polymorphism between schizophrenic patients (N = 178) and controls (N = 100). When patients were divided according to sex, or presence or absence of family history, the differences were still not significant. Our study does not support the contention that the Ser9Gly polymorphism of the DRD3 gene plays a major role in schizophrenia. Am. J. Med. Genet. 74:40–43, 1997. © 1997 Wiley-Liss, Inc.     

Toll-like receptor 4 gene Asp299Gly polymorphism in myocardial infarction: A meta-analysis of 15,148 subjects

It remains controversial regarding the association between toll-like receptor 4 (TLR4) gene Asp299Gly (+896 A/G) polymorphism and myocardial infarction (MI) risk. Thus, a large-scale meta-analysis evaluating the potential association between this gene variant and MI risk is required. PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar were searched until February 6, 2013. All the statistical tests were performed using Stata 11.0. Nine articles involving 10 studies were included in the final meta-analysis, covering a total of 8299 MI cases and 6849 controls. Overall, no significant association was found between the TLR4 gene Asp299Gly polymorphism and MI risk (G allele vs. A allele: OR = 0.95, 95% CI = 0.74–1.22, p = 0.71; G/G vs. A/A: OR = 1.03, 95% CI = 0.54–1.98, p = 0.93; G/G vs. A/G + A/A: OR = 1.05, 95% CI = 0.55–2.03, p = 0.87; G/G + A/G vs. A/A: OR = 0.92, 95% CI = 0.75–1.13, p = 0.42). In the subgroup analysis based on source of controls, there was also lack of evidence for significant association between the TLR4 gene Asp299Gly polymorphism and MI risk. In summary, the present meta-analysis indicated that the TLR4 gene Asp299Gly polymorphism was not associated with MI risk.     

Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)_n repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)_n repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z = 1.91, p = 0.055). An excess of non-transmissions was detected for the 150 and 152 bp alleles (Z = −2.26, p = 0.023; Z = −2.20, p = 0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p = 0.011), and lower effort (p = 0.008), activation (p = 0.008) and attention (p = 0.01) cluster scores. We did not replicate association findings in the case–control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)_n repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.     

Association study between a functional polymorphism of FK506-binding protein 51 (FKBP5) gene and personality traits in healthy subjects

Previous studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. FK506-binding protein 51 (FKBP51 or FKBP5) is a co-chaperone of heat-shock protein 90, and plays an important role in the negative feedback regulation of HPA axis function. It has been reported that a C/T single nucleotide polymorphism in the intron 2 of FKBP5 gene (rs1360780) affects FKBP5 protein levels and cortisol response to dexamethasone and psychological stress tests. Therefore, it is hypothesized that the FKBP5 polymorphism affects personality traits. In the present study, we studied the association between this polymorphism and personality traits in 826 Japanese healthy subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the FKBP5 genotype was detected by a real-time PCR and cycling probe technology for SNP typing. In total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (HA) (p = 0.043) and lower scores of cooperativeness (CO) (p = 0.019) compared to that without the T allele. The T allele was associated with higher scores of HA in females (p = 0.020) and lower scores of CO in males (p = 0.015). The present study thus suggests that the FKBP5 polymorphism affects HA and CO in healthy subjects, with gender specificity.     

传统抗精神病药物所致迟发性运动障碍的药理遗传学初步研究

目的：进一步探讨多巴胺D2、D3受体（dopamine D2,D3 receptor,DRD2,DRD3)功能基因多态性与迟发性运动障碍(tardive dyskinesia,TD）的相关性及各候选基因，同时包括五羟色胺2C受体（5－hydroxytryptamine 2C receptor,HTR2C）和锰超氧化物歧化酶（manganese superoxide dismutase,MnSOD）基因的相互作用对TD发生的影响。方法：使用异常不自主运动量表（abnormal involuntary movement scale,AIMS)评定精神分裂症（schizophrenia,CSH)患者有无TD及其严重程度，并采用简明精神病评定量表评定患者精神症状；应用聚合酶链反应－限制性片段长度多态性技术分析TD组和非TD组各候选基因等位基因和（或）基因型分布频率及其结合分布频率，并分析对AIMS总分值的影响。结果：各候选基因在SCH患者组以及TD和非TD组基因型分布均符合Hardy-Weinberg平衡定律；TD组HTR2C基因－697C（突变型）等位基因频率高于非TD组，差异有显著性（P＜0．05）；DRD2基因Taq I A1/A2、DRD3基因Ser9Gly和MnSOD基因Ala-9Val等位基因频率和基因型分布在TD组与非TD组之间差异均无显著性（P＞0．05）；仅DRD3突变型（Gly）和MnSOD野生型（Val）结合分布频率高于其它结合型，差异有显著性（P＜0．05）；但上述各候选基因不同等位基因和（或）基因型亚组间的临床学资料和AIMS总分值（TD值）差异均无显著性（P＞0．05）。结论：HTR2C基因启动区－697G→C单碱基置换可能是中国汉族男性SCH患者TD发生的易感因素；而SCH患者若同时携带DRD3基因9Gly突变型和MnSOD基因－9Val野生型等位基因可能增加了TD的易感性。     

CTLA-4 polymorphisms and susceptibility to inflammatory bowel disease: A meta-analysis

Objective

The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) polymorphisms are associated with susceptibility to ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

The authors conducted a meta-analysis on associations between CTLA-4 +49 A/G, −318 C/T, CT60 A/G polymorphisms, and (AT)n repeat in the 3′ untranslated region (UTR) and UC and CD susceptibility.

Results

A total of 15 comparison studies were considered in our meta-analysis. Meta-analysis revealed no association between UC and the CTLA-4 +49 G and CTLA-4 −318 T alleles in all subjects (OR = 0.982, 95% CI = 0.851–1.1339, p = 0.804; OR = 0.500, 95% CI = 0.223–1.124, p = 0.094). No association was found between UC and the CTLA-4 CT60 A/G polymorphism in Europeans. However, a significant association was observed between the longer allele (?118 bp) of the (AT)n and UC in Asian population (OR = 6.073, 95% CI = 4.246–8.684, p = 1.0 × 10⁻⁹). Meta-analysis of the CTLA-4 +49 A/G, −318 C/T, CT60 A/G polymorphisms showed no association with CD.

Conclusions

This meta-analysis demonstrates that the CTLA-4 (AT)n repeat in 3′ UTR may be associated with susceptibility to UC in Asians, while no association was found between the CTLA-4 +49 A/G, −318 C/T, and CD60 A/G polymorphism and susceptibility to UC and CD.     

Lead and Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms: A meta-analysis

This meta-analysis examined the association between Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms and lead exposure in children and adolescents. Thirty-three studies published between 1972 and 2010 involving 10,232 children and adolescents were included. There was a small to medium association between inattention symptoms and lead exposure (r = .16, k = 27, p < .001) and a similar association between hyperactivity/impulsivity symptoms and lead exposure (r = .13, k = 23, p < .001). There was significant heterogeneity among the effect sizes for both inattention symptoms and for hyperactivity/impulsivity symptoms, with studies using hair analysis to assess lead burden yielding substantially larger effect sizes than those using other methods. Excluding the hair analysis studies, the average rs were .14 for inattention (k = 23, p < .001) and .12 for hyperactivity/impulsivity (k = 21, p < .001). Overall, the relation between lead exposure and ADHD symptoms was similar in magnitude to the relation between lead exposure and decreased IQ and between lead exposure and conduct problems.     

CD226 Gly307Ser association with multiple autoimmune diseases: A meta-analysis

Background

Recently, there has been increasing evidence shown that a non-synonymous exchange (Gly307Ser/rs763361) of the CD226 gene on chromosome 18q22 is linked to several autoimmune diseases (ADs) including type 1 diabetes (T1D), celiac disease (CED), rheumatoid arthritis (RA), multiple sclerosis (MS), Grave’s disease, Wegener’s granulomatosis (WG), psoriasis, and primary sicca syndrome (pSS). Taking into consideration that different autoimmune diseases may share some common pathogenic pathways and in order to assess the overall relationship between CD226 Gly307Ser (rs763361) polymorphism and multiple autoimmune diseases, we performed this meta-analysis.

Method

All eligible case-control studies were searched in the US National Library of Medicine’s PubMed and Embase database. Crude odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association.

Results

7876 cases and 8558 controls from 7 published studies which were selected from 149 articles identified by a search of the US National Library of Medicine’s PubMed and Embase databases for the period up to 25th April 2012. The total OR for ADs associated with the T allele was 1.19 (95%CI = 1.12–1.27) by random effects model. Significantly increased risks were also observed in the South American (OR = 1.72, 95%CI = 1.34–2.20), Asian (OR = 1.46, 95%CI = 1.01–2.10), and European (OR = 1.29, 95%CI = 1.07–1.58). Similarly, significant associations were observed in two genetic models (OR = 1.41, 95%CI = 1.23–1.62 in a codominant model; OR = 1.33, 95%CI = 1.18–1.50 in a recessive model).

Conclusion

This meta-analysis provided evidence that CD226 Gly307Ser (rs763361) is significantly associated with the risk of multiple autoimmune diseases.     

Association of functional variants in the dopamine D2-like receptors with risk for gambling behaviour in healthy Caucasian subjects

Pathological gambling (PG) is an impulse control disorder with suggestive genetic vulnerability component. We evaluated the association of genetic variants in the dopaminergic receptor genes (DRD1-3s) with risk for gambling in healthy subjects using the Canadian Problem Gambling Index (CPGI). Healthy Caucasian subjects who had gambled at least once in their lifetime (n = 242) were included in the analysis. Gender was not associated with the CPGI, while younger age was associated with higher CPGI scores. We have found that none of the single polymorphisms investigated on DRD1 and DRD3 were associated with CPGI scores in healthy subjects. However, we observed trends for association on the TaqIA/rs1800497 polymorphism (P = 0.10) and the haplotype flanking DRD2 (G/C/A rs11604671/rs4938015/rs2303380; P = 0.06). Both trends were associated with lower CPGI score. Our results provide further evidence for the role of dopamine D2-like receptor in addiction susceptibility.     

Genetic variants of the BDNF and DRD3 genes in bipolar disorder comorbid with anxiety disorder

Background

The high comorbidity rate between bipolar disorder (BP) and anxiety disorder (AD) has been studied in depth. This comorbidity is not as high in Han Chinese in Taiwan. Therefore, we explored the genetic effects BP comorbid with AD.

Methods

We recruited 1316 participants: 286 with BP-I, 681 with BP-II, and 349 healthy Controls. Genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

The DRD3 Ser9Gly polymorphism was associated with BP-II comorbid with AD (BPII^+AD), and the BDNF Val66Met polymorphism was associated with BP-I comorbid with AD (BPI^+AD). An interaction between the Val/Val genotype of the BDNF Val66Met and Gly/Gly polymorphism of the DRD3 Ser9Gly was found in BPII^+AD, but not in BP-II not comorbid with AD (BPI^−AD) compared with healthy Controls.

Limitation

The low comorbidity rate of AD in both BP subtypes, especially BP-I, limit generalizing our findings.

Conclusion

The involvement of the dopaminergic pathway in AD was confirmed, particularly with BP-II rather than BP-I. Because the Val/Val genotype of the BDNF Val66Met polymorphism, rather than the other two polymorphisms, has been associated with anxiety, it seems to affect BP-I comorbid with AD without the involvement of the DRD3 Seg9Gly polymorphism, but may modify the involvement of DRD3 Gly/Gly in BP-II comorbid with AD.     

Polymorphism C in the serotonin transporter gene (SLC6A4) in questionable dementia and Alzheimer's disease

The promoter region of the serotonin transporter gene (SLC6A4) shows a 22-bp tandem repeat polymorphism, indicated as polymorphism C, that has been associated to depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding its association with Alzheimer's disease (AD). No data were reported regarding its association with questionable dementia (QD). In this study we investigate for polymorphism C in the SLC6A4 gene 302 elderly subjects with a clinical diagnosis of AD (n = 105), QD (n = 88) and no cognitive impairment (n = 114) attending a geriatric ward. A community-dwelling sample of 390 healthy subjects was also included in the analysis. A significant higher prevalence of the C16/C16 genotype in AD than in QD was observed (37.14% vs. 3%; p = 0.041, OR 2.001, 95%CI 1.018–4.024), while no differences in the C16/C14 and C14/C14 genotypes as well as in the estimated allele frequencies were found. No further differences among the three groups of subjects were found, also when they were compared with the community-dwelling sample. These findings suggest that SLC6A4 gene variation may have only a minor role, if any, in AD or QD.     

Allelic association analysis of the dopamine D2, D3, 5-HT2A, and GABA(A)gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects

Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABA(A)gamma2, and the serotonin transporter (5-HTT) were analyzed for association with heroin abuse. We examined three polymorphisms (promoter - 141DeltaC, Ser311Cys, and TaqI) in the DRD2 gene, one polymorphism (Ser9Gly) in the DRD3 gene, two polymorphisms (promoter - 1438G/A and T102C) in the HTR2A gene, two polymorphisms (VNTR and Del/Ins) in 5-HTT gene, and one polymorphism (G3145A) in GABA(A)gamma2 gene in 121 Chinese heroin addicts and 194 controls. None of the polymorphisms differed significantly for allele, genotype, or haplotype frequencies, except for the DRD2 promoter polymorphism - 141DeltaC (genotype-wise and allele-wise, P = 0.05, uncorrected). An additional 344 subjects with heroin abuse and 104 controls were investigated for the - 141DeltaC polymorphism. In the second sample, there were no significant difference of genotype or allele frequencies between subjects with heroin abuse and normal controls. When we divided the sample by route of administration into nasal inhalers and IM or IV injectors, however, it produced a significant difference between inhalers of heroin and controls (genotype-wise, P = 0.006, allele-wise, P = 0.016) but not for injectors of heroin (genotype-wise, P = 0.81, allele-wise, P = 0.69). We also found that LD between all polymorphisms we examined in the gene was weak, possibly explaining why we see association of this polymorphism with heroin abuse but not with other markers in the gene. Overall our results indicates that the HTR2A, 5-HTT, DRD3 and GABA(A)gamma2 genes are not likely to be a major genetic risk factor for heroin abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter - 141DeltaC polymorphism.     

Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and SLE.

Results

A total of 19 studies involving 2828 SLE patients and 4008 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism revealed an association between SLE and the IL-10-1082 G allele (odds ratio [OR] = 1.158, 95% confidence interval [CI] = 1.051–1.276, p = 0.003). Stratification by ethnicity indicated an association between the IL-10-1082 G allele and SLE in Europeans (OR = 1.160, 95% CI = 1.039–1.296, p = 0.008). Meta-analysis stratified by ethnicity produced an association between the IL-10-819 C allele and SLE in Asians (OR = 1.308, 95% CI = 1.030–1.619, p = 0.027). Meta-analysis of the homozygous GCC/GCC haplotype failed to show a significant association with SLE in Europeans (OR = 1.223, 95% CI = 0.981–1.526, p = 0.074). However, meta-analysis of the GCC haplotype revealed a significant association with RA in all study subjects (OR = 1.402, 95% CI = 1.001–1.964, p = 0.049). Stratification by ethnicity indicated an association between the GCC haplotype and SLE in Europeans (OR = 1.656, 95% CI = 1.087–2.523, p = 0.019), but not in Asians (OR = 1.100, 95% CI = 0.703–1.721, p = 0.677). Meta-analysis of homozygous ATA/ATA haplotype failed to show a significant association with SLE in overall and European groups. However, meta-analysis of the ATA haplotype revealed a significant association with SLE in all study subjects (OR = 1.516, 95% CI = 1.039–2.213, p = 0.031) and Asians (OR = 2.580, 95% CI = 2.086–3.192, p < 1 × 10⁻⁹), but not in Europeans (OR = 1.233, 95% CI = 0.816–1.862, p = 0.320).

Conclusions

This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.     

Association between CTLA-4 polymorphisms and susceptibility to Celiac disease: A meta-analysis

Objective

The study explored whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Celiac disease (CD).

Methods

A meta-analysis was conducted on the associations between the CTLA-4 CT60 A/G, +49 A/G, −318 C/T polymorphisms and CD using allele contrast, a recessive model, a dominant model, and homozygote contrast.

Results

Thirteen separate comparison studies were considered in the meta-analysis consisting of 5072 patients with CD and 13,462 controls. All subjects were Europeans. Meta-analysis of the CTLA-4 CT60 A/G polymorphism showed an association between CD and the CTLA-4 CT60 G allele in all subjects [Odds ratio (OR) = 1.160, 95% Confidence interval (CI) = 1.104–1.219, p < 1.0 × 10⁻⁹). Meta-analysis using the recessive model also revealed an association between CD and the CTLA-4CT60 GG genotype (OR = 1.331, 95% CI = 1.093–1.620, p = 0.004). Furthermore, analyses using the dominant model and homozygote contrast showed the same pattern as that shown by the CTLA-4CT60 G allele. Meta-analysis of the CTLA-4 +49 A/G polymorphism showed no association between CD and the CTLA-4 +49 G allele in all subjects (OR = 0.992, 95% CI = 0.872–1.129, p = 0.907). Meta-analysis using the recessive, dominant model, and homozygote contrast showed the same pattern as that shown by the CTLA-4 +49 Gallele. Meta-analysis of the CTLA-4 −318 C/T polymorphism showed no association between CD and the CTLA-4 −318 T allele in all subjects (OR = 1.018, 95% CI = 0.813–1.275, p = 0.877).

Conclusions

The CTLA-4 CT60 A/G polymorphism was associated with CD susceptibility, but no association was found between CTLA-4 +49 A/G and −318 C/T polymorphisms and CD in Europeans.     

Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

Association between apolipoprotein E gene polymorphism and the risk of vascular dementia: A meta-analysis

It remains controversial regarding the association between Apolipoprotein E (ApoE) gene polymorphism and the risk of vascular dementia (VaD). The present meta-analysis was performed to derive a more precise estimation of the relationship. The meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 29 studies included 1763 VaD cases and 4534 controls were identified. The results showed evidence for significant association between ApoE ?4 mutation and VaD risk (for ?3/?4 vs. ?3/?3: OR = 1.65, 95% CI = 1.40–1.94, p-value < 0.00001; for ?4/?4 vs. ?3/?3: OR = 3.17, 95% CI = 2.09–4.80, p-value < 0.00001; for ?4 allele vs. ?3 allele: OR = 1.72, 95% CI = 1.40–2.12, p-value < 0.00001). The similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests an association between ApoE ?4 mutation and increased risk of VaD. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution.