IL-8 (-251 A/T) and CXCR2 (+1208 C/T) gene polymorphisms and risk of multiple sclerosis in Iranian patients

IL-8 plays important roles in CNS development, modulation of neuronal survival and excitability. Among IL-8 receptors, only CXCR2 is known to be present in the brain. The ability of individuals in producing IL-8 is partially determined by IL-8 -251 A/T polymorphism. Therefore, the aim of the present study was to investigate the association between IL-8 -251 A/T and CXCR2 +1208 C/T gene polymorphisms and susceptibility to multiple sclerosis (MS). Two hundred and twenty-three MS patients and 319 healthy and ethnic matched controls were included in this study. IL-8 promoter (-251 A/T) and CXCR2 (+1208 C/T) gene polymorphisms were genotyped via allele specific PCR (AS-PCR) method. A significant difference was found in IL-8 -251 A/T polymorphism between MS patients and controls (p = 0.04). This deference was a result of a higher incidence of the low producer allele of IL-8 (T allele) in MS patients compared to controls. However, there was no significant association between different clinical findings (EDSS score, progression index, disease onset age, and the type of disease) and IL-8 -251 A/T polymorphism. Furthermore, no significant association existed between CXCR2 +1208 C/T polymorphism and MS susceptibility or different clinical parameters in patients. In summary, carriers of IL-8 -251 T allele may have increased susceptibility to MS because of their differences in neuron survival or increased chances of viral persistence compared to carriers of A allele.     

Single nucleotide polymorphism and haplotype association of the interleukin-8 gene with nasopharyngeal carcinoma

The cytokine interleukin-8 (IL-8) may play a role in the pathogenesis of nasopharyngeal carcinoma (NPC) through the modulation of tumor immune response or enhanced angiogenesis. Polymorphism of IL-8 gene, which may affect the production level of cytokine, has been inversely associated with a number of cancers. To test this hypothesis, we investigated the relationship of IL-8 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-8 gene -845 T/C, -738 T/A, -353 A/T, -251 A/T and +678 T/C in 280 patients with NPC and 290 age and sex matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers method (PCR-SSP). There were significant differences in the genotype and allele distribution of -251 A/T polymorphism of the IL-8 gene among cases and controls. The -251 AA and AT genotypes were associated with a significantly increased risk of NPC as compared with the -251 TT genotypes (OR=1.820, 95% CI, 1.120-2.959, P=0.015 and OR=1.590, 95% CI, 1.104-2.290, P=0.013, respectively). Haplotype analysis revealed that the homozygosity of the AAT haplotype (defined by SNPs at positions -353, -251 and +678) of IL-8 gene conveys the highest risk for NPC compared with the homozygosity for the TTC haplotype (OR=1.396; 95% CI, 1.064-1.831; P=0.016). The -251 A/T polymorphism of IL-8 and its haplotype are associated with NPC in a Chinese population. Our data suggests that IL-8 gene may play a role in the development of NPC.     

Association and interaction of the TNF-alpha gene with other pro- and anti-inflammatory cytokine genes and HLA genes in patients with type 1 diabetes from North India

Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where major histocompatibility complex (MHC) genes and the insulin-linked polymorphic region have been shown to play major roles. We report here an integrated effect of tumor necrosis factor (TNF) alpha with other cytokine genes. The TNF-alpha-308 GA and AA (high secretor) polymorphisms were significantly increased in the patients with T1D (n = 235) [P < 7 x 10(-6), odds ratio (OR) = 3.04, 95% confidence interval (CI) = 1.8-5.3] compared with the controls (n= 128). The variants of interferon-gamma (IFN-gamma) (A(+874)T), interleukin (IL)-6 (G(-174)C), IL-10 (A(-1082)G, T(-819)C, C(-592)A) and transforming growth factor (TGF) beta1 (T(cdn10)C, G(cdn25)C) did not show a significant difference between patients and controls. However, simultaneous presence of TNF-alpha-308 GA+AA along with both high and low secretor genotypes of IFN-gamma (P < 0.003) was significantly increased in patients. Simultaneous presence of TNF-alpha-308 GA + AA along with high secretor genotypes of IL-6 (P < 0.0001, OR = 2.61, 95% CI = 1.5-4.56), IL-10 (P < 0.0001, OR = 4.26, 95% CI = 1.9-10.1) and TGF-beta1 (P < 0.00004, OR = 2.8, 95% CI = 1.6-4.86) was also significantly increased in patients with T1D. Low secretor genotype of TNF-alpha-308 GG along with low secretor genotypes of IFN-gamma (P < 0.001, OR = 0.465, 95% CI = 0.28-0.77), high secretor genotypes of IL-6 (P < 0.000004, OR = 0.76, 95% CI = 0.227-0.621) and TGF-beta1 (P < 0.000006, OR = 0.336, 95% CI = 0.198-0.568) was protective. The TNF-alpha-308 G allele was in linkage disequilibrium (LD) with the human leukocyte antigen (HLA)-B*0801-DRB1*0301 haplotype, while TNF-alpha-308 A allele was in LD with the HLA-B*5001-DRB1*0301 and B*5801-DRB1*0301 haplotypes, suggesting that the effect of TNF-alpha -308 A allele is not because of its being in LD with any HLA alleles, but because of its functional role and its integrated effect with other cytokines.     

IkappaBalpha promoter polymorphisms in patients with rheumatoid arthritis

To investigate the role of inhibitor of kappaBalpha promoter polymorphisms in the pathogenesis of rheumatoid arthritis (RA), 140 patients with RA and 115 healthy controls were enrolled in this study. The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length polymorphisms method. In comparison with IkappaBalpha-826 C/C, the genotype frequency of IkappaBalpha-826 C/T was significantly higher in the patients with RA than that of the controls (P = 0.009, OR = 2.0, 95% CI = 1.2-3.4). The allele frequency of IkappaBalpha-826 T was also significantly increased in patients with RA when compared with that of the controls (P = 0.027, OR = 1.6, 95% CI = 1.1-2.4). In comparison with IkappaBalpha-550 A/A, the genotype frequency of IkappaBalpha-550 A/T was significantly decreased in patients with RA when compared with that of the controls (P = 0.02, OR = 0.2, 95% CI = 0.06-0.8). The allele frequency of IkappaBalpha-550 A was significantly increased in patients with RA (P = 0.007, OR = 5.1, 95% = 1.4-18.2). This study also revealed that the IkappaBalpha-826 T -550 A -519 C haplotype was significantly increased in patients with RA in comparison to that of controls (P = 0.01, OR = 1.8, 95% CI = 1.1-2.8). The IkappaBalpha-826 T and -550 A alleles are associated with susceptibility to RA. Moreover, the IkappaBalpha-826 T -550 A -519 C haplotype is associated with susceptibility to RA in Taiwan.     

Association between interleukin-10 gene -592 C/A polymorphism and the risk of type 2 diabetes mellitus: A meta-analysis of 5320 subjects

Increasing evidence suggests that interleukin-10 (IL-10) gene -592 C/A polymorphism may be associated with an increased risk of type 2 diabetes mellitus (T2DM). To provide a quantitative assessment of the association between this variant and risk of T2DM, we performed this meta-analysis. Systematic searches of electronic databases PubMed, Embase, Web of Science, CBMdisc and CNKI, as well as hand searching of the references of identified articles were performed. A total of 2698 T2DM cases and 2622 controls in seven case-control studies were included in this meta-analysis. The results showed no evidence for significant association between IL-10 gene -592 C/A polymorphism and T2DM risk (for A allele vs. C allele: OR=0.94, 95% CI=0.69-1.29, p=0.69; for A/A vs. C/C: OR=0.88, 95% CI=0.39-1.98, p=0.75; for A/A vs. A/C+C/C: OR=1.04, 95% CI=0.59-1.82, p=0.89; for A/A+A/C vs. C/C: OR=1.11, 95% CI=0.73-1.69, p=0.61). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity. In summary, results from this meta-analysis suggest that the IL-10 gene -592 C/A polymorphism is not associated with T2DM risk.     

Transforming Growth Factor β1-509C/T and +869T/C Polymorphisms on the Risk of Upper Digestive Tract Cancer: A Meta-Analysis Based on 10,917 Participants

The aim of this study was to assess the relationships between transforming growth factor β1-509C/T (rs1800469) and +869T/C (rs1800470) polymorphisms and the risk of upper digestive tract cancer (UDT cancer) by using a meta-analysis. We interrogated the databases of Medline, Embase and Wanfang (Chinese literature database) (latest update; December 15, 2011). Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were used to assess the strength of the associations. In total, 20 case-control studies were included in this meta-analysis. Overall, both TGF β1-509C/T and +869T/C polymorphisms were not associated with risk of UDT cancer [-509C/T: OR (95%CI) = 1.10 (0.99-1.22) for TT vs. C carries, P(heterogeneity) = 0.10; +869T/C: OR (95%CI) = 1.04 (0.88-1.23) for CC vs. T carriers, P(heterogeneity) = 0.02]. Subgroup analyses indicated that the -509T allele was associated with increased risk of UDT cancer in population-based studies (OR = 1.16 (1.04-1.31), P(heterogeneity) = 0.31 for TT vs. C carriers) and in small sample-sized studies (OR = 1.45 (1.15-1.84), P(heterogeneity) = 0.56 TT vs. C carriers). All subgroup analyses for the TGF β1+869T/C polymorphism indicated null association except for hepatocellular carcinoma. Interestingly, both the TGF β1-509T allele and the +869C allele were associated with decreased risk of hepatocellular cancer based on limited original studies. This meta-analysis indicated that TGF β1-509C/T rather than +869T/C is a potential risk factor for UDT cancer.     

TIM3 gene polymorphisms in patients with chronic hepatitis B virus infection: impact on disease susceptibility and hepatocellular carcinoma traits

Hepatitis B virus (HBV) infection is associated with the development of acute and chronic liver diseases including hepatocellular carcinoma (HCC). T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), which negatively regulates T-cell response and mediates phagocytosis of apoptotic cells, has been implicated in HBV infection and cancers. This study explored the polymorphisms of TIM3 gene in 535 patients with HBV-related liver diseases including 213 chronic hepatitis, 178 cirrhosis and 144 HCC, 72 HBV infection resolvers and 182 healthy controls and analyzed the effects of these polymorphisms on the disease susceptibility and HCC traits. TIM3-1541C/T, -1516G/T, -882C/T, -574G/T and +4259T/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Of the five polymorphisms genotyped, the allele T-containing genotypes (GT + TT), allele T and allele T-containing haplotype (CTCGT) of -1516G/T polymorphism were more frequent in HBV patients than in controls [P = 0.005, odds ratio (OR) = 2.300, 95% confidence interval (CI): 1.294-4.088; P = 0.004, OR = 2.266, 95% CI: 1.297-3.962; and P = 0.005, OR = 2.203, 95% CI: 1.260-3.854, respectively]. The allele T-containing genotypes and allele T of -1516G/T were associated with HCC tumor grade (P = 0.023 and P = 0.017, respectively) and lymph node metastasis (P = 0.024 and P = 0.017, respectively). These findings suggest that -1516G/T polymorphism in the promoter region of TIM3 gene may affect the disease susceptibility and HCC traits associated with HBV infection, potentially supporting the role of Tim-3 in T-cell dysfunction and exhaustion involved in persistent HBV infection and HCC development.     

The relationship between tumour necrosis factor-α gene polymorphism and susceptibility and clearance of the persistent hepatitis B virus infection in a Chinese population: a meta-analysis

To date, many studies conducted in the Chinese population have determined the correlation between the tumour necrosis factor-α (TNF-α)-238G/A, -308G/A, -857C/T and -863C/A polymorphisms and persistent hepatitis B virus (HBV) infection. However, their results remain inconclusive. With the aim of confirming this correlation, we performed a meta-analysis of 19 studies. The dichotomous data are presented as the OR with a 95% CI. The results of our study indicate that carriers of the TNF-a-857T allele among the pooled Chinese population were more likely to show spontaneous clearance of HBV (T vs C: OR = 0.824, 95% CI = 0.713–0.953, p 0.009; TT vs CC: OR = 0.701, 95% CI = 0.507–0.970, p 0.032; TC vs CC: OR = 0.804, 95% CI = 0.683–0.947, p 0.009; TT + TC vs CC: OR = 0.835, 95% CI = 0.716–0.974, p 0.021). The TNF-a-308A allele was associated with significantly reduced persistent HBV infection risk in the Chinese (A vs G: OR = 0.585, 95% CI = 0.456–0.751, p 0.002; AG vs GG: OR = 0.519, 95% CI = 0.341–0.789, p <0.000; AA + AG vs GG: OR = 0.512, 95% CI = 0.339–0.772, p 0.001). Persistent HBV infection susceptibility is associated with the TNF-α-308G/A gene polymorphism in the Chinese population, whereas HBV clearance is associated with the TNF-α-857C/T gene polymorphism.     

Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus

Several lines of evidence suggest interleukin-10 gene (IL-10) is a candidate gene in susceptibility to systemic lupus erythematosus (SLE). We investigated the association of IL-10 promoter single-nucleotide polymorphisms (SNPs) (-3575T/A, -2849G/A, -2763C/A, -1082A/G, -819T/C and -592A/C) and microsatellites (IL10.R, IL10.G) with SLE in 554 Hong Kong Chinese patients and 708 ethnically matched controls. Six haplotypes (hts) were identified from the SNPs. The genotype distribution of the ht1 (T-C-A-T-A), which is associated with low IL-10 production, was different in patients and controls (P=0.009). The homozygous genotype of non-ht1 was significantly increased in patients (P=0.009, odds ratio (OR)=1.80, 95% CI: 1.15-2.82). The frequency of IL10.G4 of IL10.G was also significantly increased in patients (P=0.017, OR=2.53, 95% CI: 1.18-5.40). We found that the homozygous non-ht1 combined with short allele (CA repeat number < or =21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27-13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26-7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62-1.78, P=0.848). The frequency of non-ht1 was significantly increased in patients with serositis (P<0.0001, OR=2.42, 95% CI: 1.55-3.80). In conclusion, the high expression promoter genotype is associated with SLE in Chinese.     

Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease

Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.     

Association of -592C/A, -819C/T and -1082A/G interleukin-10 promoter polymorphisms with idiopathic recurrent spontaneous abortion

Increasing evidence supports a role for altered T helper 1 (Th1)-Th2 cytokine balance in idiopathic recurrent spontaneous abortion (RSA). The aim of this study was to investigate the association of the interleukin 10 (IL-10) promoter polymorphisms -592C/A, -819C/T and -1082A/G with RSA. Women (n = 350) with at least three consecutive spontaneous abortions (RSA cases) and 200 control women with at least two successful pregnancies were included. The frequency of the -819T allele [P = 0.05, odds ratio (OR) = 1.51], but not other single-nucleotide polymorphisms (SNPs), was higher among RSA patients. Complete linkage disequilibrium (LD) was seen between -592C and -819C and -1082G alleles, as well as between -592A and -819T and between -819C and -1082G alleles only among patients. Although the genotype frequencies (except for -819C/C) of the three polymorphisms were comparable between patients and controls, higher frequency of -592A/-819T/-1082A haplotype (OR = 4.01, 95% CI = 1.83-7.95) was seen in cases versus controls. Regression analysis indicated that, after adjusting for potential variables, -592C/A (OR = 3.32, 95% CI = 1.76-6.27) and -819C/T (OR = 5.06, 95% CI = 2.59-9.91) were associated with exclusively early but not exclusively late RSA, where negative association for both was noted. This supports the notion of involvement of IL-10-592C/A and -819C/T polymorphisms as inherited risk factors of idiopathic RSA.     

Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case-control study

Aims: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. Methods: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. Results: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127-4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160-2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). Conclusion: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS.     

Association of PTPN22 C1858T polymorphism and type 1 diabetes: a meta-analysis

Recently, protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism has been identified as a susceptibile gene for type 1 diabetes (T1D), but studies are inconsistence, In order to assess the association between PTPN22C1858T polymorphism and T1D based on different ethnicities, a meta-analysis was performed, including 26 studies, total of 16,240 patients and 17,997 controls. Meta-analysis was performed on T versus C, T/T+T/C versus C/C (dominant model) and T/T versus T/C+C/C (recessive model) in a fixed/random effects model. The results indicated an association between the PTPN22 C1858T polymorphism and T1D in all subjects. The overall odds ratio (OR) of T versus C using the fixed effects model was 1.948 (95% CI = 1.859～2.041, P < 0.001). After stratification by ethnicity, analysis revealed that the PTPN22 C1858T polymorphism T allele was significantly associated with T1D in Europeans, Americans (OR = 1.946, 95% CI = 1.852~2.045, P < 0.001; OR = 1.946, 95% CI = 1.690~2.242, P < 0.001, respectively). Meta-analysis of the T/T+T/C genotype and the T/T genotypes showed the same results as that shown by the PTPN22 C1858T polymorphism T allele. This meta-analysis suggests a possible association between the PTPN22 C1858T polymorphism and T1D, especially in European and American populations.     

中国汉族和维吾尔族MRC1基因多态性与肺结核病的相关性

目的 探讨中国汉族和维吾尔族人群MRC1基因多态性与肺结核病易感性的联系. 方法 应用PCR和DNA测序技术,对中国汉族454例和维吾尔族595例人群的MRC1基因的第7号外显子6个SNPs(G1186A、G1195A、T1212C、C1221G、C1303T和C1323T)基因型及基因频率分布进行检测,并进行连锁不平衡分析. 结果 中国汉族人群中G1186A位点等位基因G型分布频率在肺结核病组和正常健康组之间存在显著差异(P =0.037;OR =0.76;95％ CI:0.58～0.98);AG基因型在两组之间存在显著性差异(P ＜0.01;OR=0.57;95％ CI:0.37 ～0.87).在年龄和性别校正后,G1186A位点在显性(P＜0.01;OR=0.59;95％ CI:0.40～0.87)、超显性(P =0.045;OR =0.69;95％ CI:0.47～0.99)和加性模式(P =0.041;OR=0.76;95％ CI:0.59 ～0.99)时,与肺结核病存在显著相关性.在维吾尔族人群中G1186A位点的等位基因G的分布频率在两组之间的分布具有显著性差异(P =0.031;OR=1.29;95％CI:1.02 ～ 1.62);基因型分析发现AA基因型在两组之间也存在显著性差异(P=0.033;OR=1.64;95％ CI:1.04～2.60);在年龄和性别校正后,G1186A位点在加性模式下与肺结核病存在相关性(P=0.033;OR=1.28;95％ CI:1.02～1.61).连锁不平衡分析发现,构建的单体型GGTCCT(P=0.032;OR =0.75;95％ CI:0.57 ～0.97)和GGTCCC(P=0.044;OR=0.57;95％ CI:0.33 ～0.99)与肺结核病存在显著的相关性. 结论 MRC1基因G1186A位点与中国人群肺结核病相关.     

Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese

Interferon gamma (IFN-gamma) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-gamma activates macrophages, while IL-10 downregulates the expression of T helper type 1 cytokines, MHC class II antigens and costimulatory molecules on macrophages. Associations of IFN-gamma -179 (G/T), +874 (A/T), +875 miscrosatellite CA repeats and +4766 (C/T), and IL-10 -1082 (A/G), -819 (C/T) and -592 (C/A) with tuberculosis (TB) were investigated in 385 HIV-negative patients and 451 controls in a Hong Kong Chinese population. The frequency of a low IFN-gamma-producing +874 A/A genotype was significantly over-represented in the patient group (P<0.001, OR=3.79, 95% CI=1.93-7.45). We identified 10 alleles in the IFN-gamma CA repeats and observed a significant difference in allele frequency distribution between patients and controls (P<0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (P<0.001, OR=4.56, 95% CI=2.21-9.43) as observed in +874 A/A genotype. Weak associations of the IL-10 GCC/- genotype (P=0.04) and the low IFN-gamma-producing A/A genotype (P=0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.     

Inhibitors of kB-like gene polymorphisms in rheumatoid arthritis

OBJECTIVES: To investigate the role of inhibitor of kB-like (IkBL) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: One hundred and twenty-nine patients with RA and 110 healthy controls were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing was used to determine the polymorphisms of IkBL -421 8T/9T, -324 C/G, -262 A/G, and -62 A/T. PCR/restriction fragment length polymorphism was used to determine the IkBL +738 T/C polymorphisms. RESULTS: The genotype distribution of IkBL -421 was significantly different between DR4(+) RA patients and DR4(+) controls (p = 0.02). The allele frequency of IkBL -421 8T was significantly higher in DR4(+) RA patients than in DR4(+) controls (p = 0.004, OR = 7.2, 95% CI = 1.7-29.2). The allele carriage frequency of IkBL -421 8T also tended to be increased in DR4(+) RA patients in comparison with DR4(+) controls (p = 0.07, OR = 14.6, 95% CI = 1.4-147.0). We also found that the allele frequency of IkBL -62 T was significantly higher in RA patients than in controls (p = 0.04, OR = 1.5, 95% CI = 1.1-2.1). The allele carriage frequency of IkBL -62 T tended to be increased in RA patients (p = 0.08, OR = 1.7, 95% CI = 1.0-3.0). The estimated haplotype frequency of IkBL -421 8T/-62 T tended to be increased in RA patients compared with controls (p = 0.07, OR = 1.4, 95% CI = 1.0-2.0). CONCLUSION: The IkBL -62 T may be associated with the development of RA in Taiwan. The IkBL -421 8T may also be related to susceptibility to RA in HLA-DR4(+) individuals. This study shows that the estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility to RA in Taiwan.     

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility

Aim: Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. Methods: 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. Results: The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). Conclusion: we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.     

Infants' MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: A meta-analysis based on 17 case-control studies

Methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, is thought to be involved in the development of nonsyndromic orofacial clefts (NSOC). However, conflicting results have been achieved when evaluating the associations between infants' MTHFR C677T and A1298C polymorphisms and the risk of NSOC. To obtain more precise estimations of these associations, a meta-analysis recruiting 17 case-control studies was performed. Among Asians we found that CT heterozygote, TT homozygote, and CT/TT of infants' MTHFR C677T variant could contribute to elevated risks of NSOC, compared with CC wild-type homozygote (OR?=?1.741, 95% CI?=?1.043-2.907 for CT vs. CC, OR?=?2.311, 95% CI?=?1.313-4.041 for TT vs. CC, and OR?=?1.740, 95% CI?=?1.051-2.882 for CT/TT vs. CC, respectively). Similar effect was also observed on MTHFR 677T T allele, when using C allele as a reference in Asians (OR?=?1.420, 95% CI?=?1.191-1.693, for T allele vs. C allele). Furthermore, in stratified analysis by types of disease, CT/CC was suggested to confer decreased susceptibility to CL/P under recessive genetic model (OR?=?0.854, 95% CI?=?0.730-1.000). For MTHFR A1298C, the MTHFR 1298C allele in the case group of Caucasians was significantly lower than that in the control group, suggesting a protective effect against NSOC in Caucasian populations (OR?=?0.711, 95% CI?=?0.641-0.790, for C allele vs. A allele). In conclusion, the meta-analysis provided confirmative evidences that infants' MTHFR C677T and A1298C polymorphisms were involved in the development of NSOC. ? 2012 Wiley Periodicals, Inc.     

No association of ERCC1 C8092A and T19007C polymorphisms to cancer risk: a meta-analysis

ERCC1 (excision repair cross complementation group 1) is a subunit of the nucleotide excision repair complex, which can perform DNA strand incision correction of DNA damage. Association studies on the ERCC1 polymorphisms (C8092A and T19007C) in cancer had shown conflicting results. We performed a meta-analysis from all eligible case-control studies to assess the purported associations. Overall, the 19007C allele (3 853 patients and 4 349 controls) showed no significant effect on cancer risk compared to 19007T allele (P=0.39, odds ratio (OR)=0.95; 95% confidence interval (CI) 0.85-1.06, P(heterogeneity)=0.001) in all subjects. Meta-analysis under other genetic contrasts did not reveal any significant association of T19007C to cancer in all subjects, Caucasians and Asians. The 19007C allele (2 279 patients and 2 808 controls) showed no significant effect on lung cancer risk compared to 19007T allele (P=0.72, OR=0.94, 95% CI 0.69-1.29, P(heterogeneity)=0.0001) in all subjects. No significant effect of 8092A allele (3 865 patients and 3 750 controls) on cancer risk in all subjects (P=0.85, OR=1.01, 95% CI 0.94-1.08, P(heterogeneity)=0.92) and in Caucasians and Asians compare to 8092C. No evidences of association of C8092A (501 patients and 620 controls) to squamous cell carcinoma were found. The accumulated evidence indicated ERCC1 T19007C and C8092A might not be risk factors for cancer. Significant between-study heterogeneity existed in T19007C, which arose from a study showing significant protecting effect of 19007C allele compare to 19007T allele in smokers. More studies based on larger, stratified case-control population should be required to further evaluate the role of ERCC1 C8092A and T19007C polymorphisms in different cancer, especially in smokers.