Interleukin-18 promoter -607 C/A and -137 G/C polymorphisms and susceptibility to type 1 diabetes: A meta-analysis

ObjectiveThe aim of this study was to determine whether the functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518) and -137 G/C (rs187238) polymorphisms are associated with susceptibility to type 1 diabetes (TID).MethodsA meta-analysis was conducted to assess the associations between the IL-18 -607 C/A and -137 G/C polymorphisms and T1D in overall and by ethnic group.ResultsA total of 6075 cases and 5744 controls from ten studies were considered in this meta-analysis. In all study subjects, the meta-analysis showed no association between T1D and the IL-18 -607 C allele (OR = 1.083, 95% CI = 0.930–1.260, p = 0.307). However, stratification by ethnicity indicated an association between the IL-18 -607 C allele and T1D in Asians (OR = 1.506, 95% CI = 1.172–1.936, p = 0.001), but not in Europeans (OR = 0.988, 95% CI = 0.808–1.209, p = 0.907). Analysis using recessive and dominant models and homozygote contrast showed the same -607 C allele pattern in Asians and Europeans. Meta-analysis of the IL-18 -137 G/C polymorphism showed no association between T1D and the IL-18 -137 G allele in all study subjects (OR = 1.066, 95% CI = 0.926–1.2289, p = 0.375). Stratification by ethnicity indicated no association between the IL-18 -137 G allele and T1D in Europeans and Asians (OR = 1.021, 95% CI = 0.961–1.085, p = 0.504; OR = 0.851, 95% CI = 0.5821–1.245, p = 0.406).ConclusionsOur meta-analysis demonstrates that the IL-18 -607 C/A polymorphism may be associated with susceptibility to T1D in Asians, but not in Europeans.     

FCRL3 gene polymorphisms as risk factors for rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. As a member of FCRLs clusters, Fc receptor-like 3 (FCRL3) has been recognized as a neoteric autoimmune activation factor for RA. The aim of our study is to evaluate the correlation between four single-nucleotide polymorphisms (SNPs) on FCRL3 and RA risk in a Chinese Han population.Material and methodsThe hospital-based case-control study included 630 RA patients together with 696 healthy individuals as the control group and all subjects are Chinese ancestry. Four tagging single-nucleotide polymorphisms (tag-SNPs) on FCRL3 were selected and genotyped by TaqMan assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to evaluate the correlations between FCRL3 polymorphisms and RA. A systematic meta-analysis was also carried out based on the present study and previously published studies to further examine the association between FCRL3 variations and RA risk.ResultsSignificant association was found between −169T/C SNP and RA risk (CC vs. TT, OR = 1.62, 95% CI = 1.18–2.22; TC/CC vs. TT, OR = 1.47, 95% CI = 1.18–1.84; C vs. T, OR = 1.32, 95% CI = 1.12–1.54). Apart from that, mutations of −169T/C was significantly correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positive status. The meta-analysis also suggested that −169T/C mutation might have positive correlation with risk of RA in the overall population, particularly for Asian. Stratified analysis based on clinical characteristics of RF and ACPA also provided evidence that −169T/C polymorphisms could alter phenotypes of RA.ConclusionThe FCRL3 −169T/C variant was significantly linked with an increased RA risk in the Chinese Han population. Moreover, this meta-analysis also provides notion that −169T/C variant could act as a susceptible factor for RA. However, further investigations about the functional impacts of this polymorphism are essential to confirm the above conclusions.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

Association between KIR gene polymorphisms and rheumatoid arthritis susceptibility: A meta-analysis

ObjectivesThe results of studies on association between KIR (killer cell immunoglobulin-like receptors) polymorphisms and susceptibility to RA (rheumatoid arthritis) are inconsistent. To comprehensively evaluate the effect of KIR polymorphisms on the risk of RA, a meta-analysis was carried out.MethodsThe Web of Science, PubMed, the Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to select studies on the association between KIR polymorphisms and RA. The odds ratio (OR) with 95% confidence interval (95%CI) was obtained.ResultsNine qualified case–control studies were included in this meta-analysis. The results showed there were two positive associations of 2DL1, 2DS1 (OR_2DL1 = 2.20, 95%CI = 1.20–4.01, P_raw = 0.01, P_FDR = 0.03; OR_2DS1 = 1.84, 95%CI = 1.19–2.85, P_raw = 0.006, P_FDR = 0.018) and one negative association of 2DL3 (OR_2DL3 = 0.42, 95%CI = 0.22–0.79, P_raw = 0.006, P_FDR = 0.018) with susceptibility to RA in East Asians, but not in Caucasians.ConclusionThe current meta-analysis provides evidence that 2DL3 might be a potential protective factor and 2DL1, 2DS1 might be risk factors for RA in East Asians but not in Caucasians.     

Association between interleukin 1 receptor antagonist gene 86-bp VNTR polymorphism and sepsis: A meta-analysis

ObjectiveMany studies have focused on the relationship between interleukin 1 receptor antagonist (IL1RN) gene 86-bp VNTR polymorphism and sepsis, but the results remain inconsistent. Thus, a meta-analysis was carried out to derive a more precise estimation of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality.MethodsRelevant publications were searched in several widely used databases and six eligible studies were included in the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between IL1RN 86-bp VNTR polymorphism and risk of sepsis and sepsis-related mortality.ResultsSignificant associations between IL1RN 86-bp VNTR polymorphism and sepsis risk were observed in both overall meta-analysis for L2 versus 22 (OR = 0.75, 95% CI = 0.59–0.94) and severe sepsis subgroup for LL + L2 versus 22 (OR = 0.67, 95% CI = 0.47–0.93). L stands for long alleles containing three to six repeats; 2 stands for short allele containing two repeats. However, no significant sepsis mortality variation was detected for all genetic models.ConclusionsAccording to the results of our meta-analysis, the IL1RN 86-bp VNTR polymorphism probably associates with sepsis risk but not with sepsis-related mortality.     

IL28B gene variants and glucose metabolism in Type 2 Diabetes

Type 2 Diabetes (T2D) develops, when β-cell insulin response fails to compensate for insulin resistance. Recent studies reported associations between the IL28B polymorphisms (rs12979860 and rs8099917) and T2D development in Hepatitis C virus (HCV) patients. To identify possible association with T2D independent from virus infection, we investigated both IL28B polymorphisms in T2D patients and healthy controls (HC). No association was found comparing the genotype and allele frequencies of both IL28B polymorphisms between T2D patients and HC. However, higher glucose levels were found in T2D patients carrying the IL28B CT/TT rs12979860 and GT/GG rs8099917 HCV risk genotypes compared to those with the protective CC and TT genotype (p = 0.06 and p = 0.02, respectively). Moreover, T2D patients with CT/TT rs12979860 HCV risk genotypes possessed significantly higher HbA1c levels than CC carriers (p = 0.04). In conclusion, the IL28B HCV risk genotypes may influence glucose homeostasis in T2D patients without HCV.     

CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population

BackgroundSingle nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).MethodsGenotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C>G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.ResultsCRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA–2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA–2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.ConclusionsCRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.     

Association of PTPN22 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

Lymphoid protein tyrosine phosphatase encoded by protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays an important regulatory role in T- and B-cell activation. This study investigated PTPN22 −1123G/C and intron 16 T/C polymorphisms in 372 patients with chronic hepatitis B virus (HBV) infection, 72 HBV infection resolvers and 273 healthy controls. Genotypic association tests between groups assuming codominant, dominant or log-additive genetic models were performed. In recessive model, PTPN22 −1123G/C genotype GG in healthy controls was more frequent than infection resolvers (P = 0.037, OR = 3.606, 95%CI = 1.079–12.053) and this genotype in HBV patients was more frequent than resolvers although the difference was not significant (P = 0.059). The PTPN22 intron 16 T/C genotype TC in cirrhosis patients was significantly higher than asymptomatic carriers (ASC) in codominant (P = 0.028, OR = 9.792, 95%CI = 1.281–74.832) and overdominant (P = 0.025, OR = 10.142, 95%CI = 1.332–77.214) models. This genotype in hepatocellular carcinoma (HCC) patients was significantly higher than ASC in codominant (P = 0.034, OR = 9.200, 95%CI = 1.176–71.990) and overdominant (P = 0.030, OR = 9.677, 95%CI = 1.241–75.442) models. These findings suggest that PTPN22 polymorphisms may predispose the chronicity or the development of cirrhosis and HCC in HBV infection.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians

ObjectiveLimited data are available on the genetics of rheumatoid arthritis (RA) in Egyptians. Therefore, we investigated whether the confirmed genetic risk factors for RA in Europeans and/or Asians contribute to RA susceptibility in Egyptians.Subjects and methodsA set of seven single-nucleotide polymorphisms (SNPs) in the vicinity of CD28, TNFAIP3, PTPN22, PADI4 and HLA-DRA were tested in a large multi-centric RA cohort in Egypt, consisting of 394 cases and 398 matched controls. Patients were stratified based on the positivity of either anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor (RF).ResultsSignificant association was evident for three SNPs in this cohort: the CD28 (rs1980422) variant showed a strong association in the whole cohort (P = 0.000119) and in seropositive subsets of the disease (P_ACPA+ = 0.004; P_RF+ = 0.0005). Upon stratification, the PTPN22 (rs2476601) and TNFAIP3(rs5029939) variants showed association only with ACPA positive (P_ACPA+ = 0.00573) and negative (P_ACPA− = 0.00999) phenotypes, respectively.ConclusionOur results suggest that CD28(rs1980422) and PTPN22(rs2476601) contribute to RA-susceptibility in Egyptians. Failure to replicate the association of PADI4(rs2240340)/(PADI4_94) in Egyptian RA patients provides further support for the notion that genetic architecture of RA is different in multiple populations of European, Asian, African, and Middle Eastern ancestries. Further investigation using large-scale studies is thus needed to maximize the power of genetic association.     

Association of inhibin α gene promoter polymorphisms with risk of idiopathic primary ovarian insufficiency in Korean women

ObjectiveThe aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic.Study designWe genotyped the INHA polymorphisms c.-16C > T (rs35118453) and c.-124A > G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI.ResultsThere were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T–G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR = 1.630, 95% CI = 1.081–2.457). Combination genotype analysis showed that the CT + TT/GG genotype frequency was higher in POI patients than in the controls (OR = 2.414, 95% CI = 1.190–4.895).ConclusionsWe provide evidence to suggest that when the two variant alleles are combined, the c.-16C > T and c.-124A > G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk.     

Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to Alzheimer's disease

No clear consensus has been reached at the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and Alzheimer's disease (AD) risk. Thus in this meta-analysis, a total of 19 case–control studies was assessed to evaluate the possible association. The data demonstrated that the frequency of T677 allele (T vs. C) was significantly associated with susceptibility to AD in all subjects (OR = 1.15, 95% CI = 1.06–1.26) and in East Asians (OR = 1.22, 95% CI = 1.08–1.39). There was statistical difference between AD patients and the controls under recessive genetic mode (CT + TT vs. CC) and homozygote comparison (TT vs. CC) in all subjects and in East Asians as well. Despite a small effect of the polymorphism on late-onset AD (LOAD) risk, MTHFR C677T polymorphism was not a major risk factor for LOAD in East Asians and Caucasians. A subgroup analysis in the subjects without APOE ?4 alleles showed T677 allele significantly increased risk of AD in all subjects (OR = 1.21, 95% CI: 1.04–1.42) and in East Asians (OR = 1.28, 95% CI: 1.06–1.55). However, no association was found in Caucasians. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing AD susceptibility in East Asians, not in Caucasians.     

Association of IL-17A and IL-17F polymorphisms with gastric cancer risk in Asians: A meta-analysis

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR = 1.61, 95% CI = 1.17–2.23, P = 0.004); A allele was significantly associated with increased GC risk compared with G allele (OR = 1.22, 95% CI = 1.06–1.41, P = 0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR = 1.40, 95% CI = 1.04–1.88, P = 0.025; CT vs. TT: OR = 1.35, 95% CI = 1.16–1.58, P < 0.001; C allele vs. T allele: OR = 1.30, 95% CI = 1.15–1.47, P < 0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis.     

Evidence of association of interleukin-23 receptor gene polymorphisms with Egyptian rheumatoid arthritis patients

BackgroundThe identification of additional genetic risk factor is an on-going process that will aid in the understanding of rheumatoid arthritis (RA) aetiology. A genome-wide association scan in Crohn’s (CD) disease highlighted the interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene. The rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients.MethodsA group of Egyptian patients with RA (n = 120) and apparently healthy persons as controls (n = 120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs.ResultsOur data emphasise that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with RA patients compared to the controls (P value = 0.001).We did not find any significant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (P value = 1.000 & 0.562 respectively).ConclusionOur results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the subgroup of patients who will benefit from the selective suppression of the IL23 signalling which would represent new perspectives toward a personalized therapy of RA patients by further studies.     

Nonclassical human leukocyte antigen (HLA-G,HLA-E,and HLA-F) in coronary artery disease

AimsSeveral evidences suggest the association between the evolution of coronary artery disease (CAD) and the development of coronary syndrome that is often associated with disrupted plaque and partial or complete thrombosis of the related artery. Because of the inflammatory nature of CAD, we investigated the human leukocyte antigen (HLA)-G, HLA-E, and HLA-F genetic polymorphisms within CAD patients and evaluated their potential association with this disease in Tunisian population.MethodsDifferent polymorphisms in HLA-G (14-bp Insertion/Deletion, +3142C/G), HLA-E (HLA-E*01:01/01:03 A/G), HLA-F (HLA-F*01:02 T/C, 01:03 C/T, 01:04 A/C) genes were typed using different laboratory techniques in a cohort of 89 CAD patients and 84 controls.ResultsA significant association was reported between the HLA-G +3142 G allele (OR = 1.64, 95% CI = 1.05–2.56, p = 0.02) and increased risk of CAD. No association was found for the other studied polymorphisms. When we considered the haplotypes, we found TDELCA and TDELGG haplotypes associated to CAD with p = 0.008 and p = 0.030, respectively, suggesting the potential interaction between HLA-G and HLA-E genes.ConclusionsOur findings indicated that the HLA-G +3142C/G polymorphism and TDELCA and TDELGG haplotypes can harbour a reliable diagnosis value for the risk of CAD development suggesting that HLA-G, -E and -F molecules might be involved in the pathogenesis of the disease. However, further studies are necessary to confirm our results.     

A meta-analysis of P2X7 gene-1513A/C polymorphism and pulmonary tuberculosis susceptibility

ObjectiveA meta-analysis was performed to determine the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.MethodsBased on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.ResultsA total of 1916 cases and 2194 controls in 10 studies were pooled together for evaluation of the overall association between P2X7-1513A/C polymorphism and susceptibility of pulmonary tuberculosis. Allele model (A vs. C: p = 0.15; OR = 0.86, 95% CI = 0.69–1.06), homozygous model (AA vs. CC: p = 0.22; OR = 0.78, 95% CI = 0.53–1.16), and heterozygous model (AC vs. CC: p = 0.23; OR = 0.80, 95% CI = 0.56–1.15) did not show decreased risk of developing pulmonary tuberculosis. Similarly, dominant model (AA + AC vs. CC: p = 0.19; OR = 0.80, 95% CI = 0.56–1.12) and recessive model (AA vs. AC + CC: p = 0.21; OR = 0.85, 95% CI = 0.66–1.10) failed to show decreased risk of developing pulmonary tuberculosis. In Indians, allele model (A vs. C: p = 0.0006; OR = 0.69, 95% CI = 0.55–0.85), and recessive model (AA vs. AC + CC: p = 0.0003; OR = 0.62, 95% CI = 0.48–0.80) indicated significant association between P2X7-1513A/C polymorphism and susceptibility to pulmonary tuberculosis.ConclusionsOur pooled data suggest a association between P2X7-1513A/C polymorphism and the prevalence of pulmonary tuberculosis among Indian populations.     

Internet health information seeking is a team sport: Analysis of the Pew Internet Survey

BackgroundPrevious studies examining characteristics of Internet health information seekers do not distinguish between those who only seek for themselves, and surrogate seekers who look for health information for family or friends. Identifying the unique characteristics of surrogate seekers would help in developing Internet interventions that better support these information seekers.ObjectiveTo assess differences between self seekers versus those that act also as surrogate seekers.MethodsWe analyzed data from the cross-sectional Pew Internet and American Life Project November/December 2008 health survey. Our dependent variable was self-report of type of health information seeking (surrogate versus self seeking). Independent variables included demographics, health status, and caregiving. After bivariate comparisons, we then developed multivariable models using logistic regression to assess characteristics associated with surrogate seeking.ResultsOut of 1250 respondents who reported seeking health information online, 56% (N = 705) reported being surrogate seekers. In multivariable models, compared with those who sought information for themselves only, surrogate seekers were more likely both married and a parent (OR = 1.57, CI = 1.08, 2.28), having good (OR = 2.05, CI = 1.34, 3.12) or excellent (OR = 2.72, CI = 1.70, 4.33) health status, being caregiver of an adult relative (OR = 1.76, CI = 1.34, 2.30), having someone close with a serious medical condition (OR = 1.62, CI = 1.21, 2.17) and having someone close to them facing a chronic illness (OR = 1.55, CI = 1.17, 2.04).ConclusionsOur findings provide evidence that information needs of surrogate seekers are not being met, specifically of caregivers. Additional research is needed to develop new functions that support surrogate seekers.     

Genetic polymorphisms in TNFSF13 and FDX1 are associated with IgA nephropathy in the Han Chinese population

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and its pathogenesis is influenced by both genetic and environmental factors. In this study, we evaluated 23 tag single-nucleotide polymorphisms (tSNPs) in 21 IgAN-associated genes, in 200 subjects with IgAN and 310 healthy gender- and age-matched unrelated control subjects with no history of renal disease or hypertension. Using the co-dominant model, we found that two genotypes of rs3803800 in TNFSF13 were associated with an increased risk of IgAN: “GA” (OR = 1.03, 95% CI = 0.71–1.51, p = 0.018) and “AA” (OR = 2.45, 95% CI = 1.29–4.65, p = 0.018). The “AA” genotype was also associated with an increased risk of IgAN in the recessive model (OR = 2.41, 95% CI = 1.30–4.46, p = 0.018), as was the genotype “AA” rs10488764 in FDX1 (OR = 1.88, 95% CI = 1.01–3.53, p = 0.048). Interestingly, we found that the allele “A” of rs3803800 in TNFSF13 is associated with a decreased risk of IgAN in females (OR = 0.43, 95% CI = 0.20–0.95, p = 0.009), but with an increased risk in males (OR = 1.78, 95% CI = 0.86–3.66, p = 0.009). Our findings, combined with previously reported results, suggest that TNFSF13 and FDX1 have potential roles in IgAN in the Han Chinese population. This information may be useful in the development of early prognostics for IgAN.     

A meta-analysis of the relationship between MYO9B gene polymorphisms and susceptibility to Crohn’s disease and ulcerative colitis

ObjectiveBoth Crohn’s disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk.MethodsThe PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR = 0.88, 95% CI = 0.82 ∼ 0.95, P = 0.001; OR = 0.82, 95% CI = 0.76 ∼ 0.89, P < 0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR = 0.85, 95% CI = 0.79 ∼ 0.91, P < 0.001; OR = 0.88, 95% CI = 0.83 ∼ 0.93, P < 0.001), but not with CD susceptibility in Caucasians.ConclusionsThis meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion.     

Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arthritis in Zahedan,Southeast Iran

In this study we aimed to evaluate the possible association of PTPN22 rs2476601 as well as epidermal growth factor receptor (EGFR) rs17337023 gene polymorphism and rheumatoid arthritis (RA) in a sample of Iranian population. This case‐control study was performed on 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood and PTPN22 rs2476601 and EGFR rs17337023 polymorphisms were determined using tetra amplification refractory mutation system–polymerase chain reaction (T‐ARMS‐PCR). The results showed that PTPN22 rs2476601 CT genotype as well as rs2476601 T allele was a risk factor for susceptibility to RA (OR=5.89 95%CI = 1.78–19.48, P = 0.004 and OR = 4.78, 95%CI = 1.59–14.35, P = 0.003, respectively). We also found that EGFR rs17337023 AT and rs17337023 TT genotypes were risk factor for susceptibility to RA (OR = 9.94 95%CI = 3.65–26.73, P < 0.001 and OR = 3.66, 95%CI = 1.46–9.15, P = 0.005, respectively). In addition the EGFR rs17337023 T allele was a risk for predisposition to RA (OR = 1.56, 95%CI=1.06‐2.30, P = 0.030). In conclusion, we found an association between PTPN22 rs2476601 and EGFR rs17337023 polymorphisms and the risk of RA in a sample of Iranian population.