Systemic Lupus Erythematosus In Europeans Research Articles

Associations of toll-like receptor polymorphisms with systemic lupus erythematosus: A meta-analysis

ObjectiveThe objective of this study was to examine whether polymorphisms in toll-like receptors 7 and 4 (TLR7 and 4) contribute to vulnerability to systemic lupus erythematosus (SLE). MethodsWe searched MEDLINE, Embase, and Web of Science for relevant articles and performed a meta-analysis to investigate the relationship between TLR7 rs179008, rs3853839, rs1790010, TLR4 rs4986791, and rs798690 polymorphisms and SLE. ResultsEighteen studies and 16 papers including 8022 patients with SLE and 9822 healthy controls were retrieved. Meta-analysis revealed that the TLR7 rs179008 T variant was not associated with SLE (OR = 1.008, 95% CI = 0.849–1.394, P = 0.504). Ethnic classification revealed no association between the TLR7 rs179008 T gene and SLE in either European or Latin American groups. Additionally, homozygous comparison, recessive, and dominant models revealed no association between the TLR7 rs179008 variant and SLE. In contrast, a significant association between SLE and the TLR7 rsrs3853839 GG + GA allele (OR = 2.135, 95% CI = 1.502–3.035, <0.001; OR = 23.20, 95% CI = 14.13–38.08, <0.001) was observed in the Arab and Asian groups. The T variant of TLR7 rsrs179010 was also associated with SLE in Asians (OR = 1.177, 95% CI = 1.048–1.321, P = 0.006). In contrast, the TLR4 rs4986791 variant was not associated with SLE in Europeans when allele, homozygous comparison, recessive, and dominant models were used. Furthermore, no association between the TLR4 rs4986790 variant and SLE risk in Europeans was found using any genomic model. ConclusionsMeta-analysis revealed that the TLR7 rs3853839 variant is associated with SLE risk in Asians and Arabs and that TLR7 rs179010 is associated with SLE in Asians. However, TLR7 rs179008, TLR4 rs4986791, and TLR rs798690 polymorphisms were not associated with SLE risk.

Association Between Signal Transducers and Activators of Transcription 4 rs7574865 Polymorphism and Systemic Lupus Erythematosus: A Meta-analysis

Objective. The purpose of this study was to determine whether the rs7574865 polymorphism of signal transducers and transcription 4 activators (STAT4) in multiple ethnic populations is associated with susceptibility to systemic lupus erythematosus (SLE). Methods. A meta-analysis on the STAT4 T allele rs7574865 polymorphism was performed in all subjects of study as well as in each ethnic population. Results. It included twenty-four manuscripts with 36 comparative studies of 22,898 SLE patients and 24,838 controls. The mean frequency of the STAT4 rs7574865 T allele was 28.5%, ranging from 14.3% to 35.7%, among the controls. T allele rates were 14.3%, 22.8%, 31.9%, 32.4%, and 35.7%, respectively in African American, European, Arab, Asian, and Latin American populations. Meta-analysis revealed a substantial correlation in all subjects between STAT4 rs7574865 and SLE (odds ratio=1.549, 95% confidence interval=1.459∼1.644, p＜0.001). Analysis after stratification of race showed a strong association between the STAT4 rs7574865 T allele and SLE in Europeans, Asians, Latin Americans, African Americans, and Arabs. Conclusion. This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism in different ethnic groups was correlated with SLE susceptibility, and that its prevalence depended on ethnicity. (J Rheum Dis 2020;27:277-284)

Association of IRF5 rs2004640 polymorphism and systemic lupus erythematosus: A meta-analysis.

This study aimed to discuss the relationship between interferon regulatory factor (IRF)5 gene rs2004640 T/G polymorphism and systemic lupus erythematosus (SLE) susceptibility. A meta-analysis was calculated on the association between rs2004640 polymorphism and SLE by allelic contrast (T vs G), additive model (TT vs GG), recessive model (TT vs TG+GG) and dominant model (TT+TG vs GG). A total of 28 comparisons were identified, including 11228 SLE cases and 14374 controls. Meta-analysis revealed a significant association between allele T and SLE in overall populations (odds ratio [OR]=1.393, 95% CI: 1.276-1.522, P<0.001). Stratification by ethnicity indicated strong associations between T allele and SLE in Asians, Europeans and Latin Americans (OR=1.256, 95% CI: 1.073-1.469, P=0.004; OR=1.338, 95% CI: 1.080-1.659, P=0.008; OR=1.853, 95% CI: 1.488-2.308, P<0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR=1.999, 95% CI: 1.442-2.771, P<0.001; OR=1.544, 95% CI: 1.009-2.362, P<0.045). In addition, we found significant associations between the dominant model and SLE in all populations and Asians (OR=1.521, 95% CI: 1.257-1.841, P<0.001; OR=1.270, 95% CI: 1.136-1.421, P<0.001). A marginal association was detected between the recessive mode and SLE in overall subjects (OR=1.480, 95% CI: 1.022-2.144, P=0.038). The current study suggested that individuals carrying rs2004640 T allele correlated with a high risk of SLE, and the IRF5 rs2004640 polymorphism was associated with SLE susceptibility.

Association between the interferon regulatory factor 5 rs2004640 functional polymorphism and systemic lupus erythematosus: an updated meta-analysis.

The aim of this study is to determine whether the functional interferon regulatory factor 5 ( IRF5) polymorphism rs2004640 is associated with susceptibility to systemic lupus erythematosus (SLE) in multiple ethnic populations. A meta-analysis was conducted on the T allele of the IRF5 rs2004640 polymorphism in all study participants as well as each ethnic population. Twenty research articles that included 28 comparative studies of 20,892 patients and 24,930 controls were included in the meta-analysis. The Asian population had a much lower prevalence of the T allele than any other study population at 28%, and the European population had the highest prevalence of the T allele at 52%. Meta-analysis showed an association between the IRF5 rs2004640 polymorphism and SLE in all participants (odds ratio = 1.472, 95% confidence interval = 1.370-1.582, p < 0.001). Analysis after stratification by ethnicity indicated that the IRF5 rs2004640 T allele is significantly associated with SLE in Europeans, Asians, Latin Americans and Arabs. This meta-analysis confirms that the IRF5 rs2004640 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.

Association between tumor necrosis factor polymorphisms and rheumatoid arthritis as well as systemic lupus erythematosus: a meta-analysis.

Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57–0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45–2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15–1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32–3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56–2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32–0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles.

Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis.

Previous studies have reported that genes relating to JAK-STAT pathway (IFIH1, TYK2 and IL-10) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P = 2.56 × 10-11, OR 1.135, 95% CI 1.094-1.179, dominant: P = 1.8 × 10-8, OR 1.203, 95% CI 1.128-1.284, recessive: P = 2.6 × 10-7, OR 1.163, 95% CI 1.098-1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans (P = 5.82 × 10-5, OR 1.434, 95% CI 1.203-1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model (P = 8.05 × 10-3, OR 1.314, 95% CI 1.074-1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model (P = 4.65 × 10-3, OR 2.623, 95% CI 1.346-5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model (P = 1.21 × 10-2, OR 1.375, 95% CI 1.072-1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P = 4.65 × 10-3, OR 1.539, 95% CI 1.142-2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.

Association of angiotensin‐converting enzyme insertion/deletion polymorphism with susceptibility to systemic lupus erythematosus: a meta‐analysis

The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism confers susceptibility to systemic lupus erythematosus (SLE)/lupus nephritis (LN). A meta-analysis was conducted on the association between the ACE I/D polymorphism and SLE/LN (when available) using: (i) the allelic contrast; (ii) the recessive; (iii) the dominant; and (iv) the additive models. A total of 27 relevant comparisons meeting the inclusion criteria were identified, involving 2718 SLE patients and 3655 controls. Meta-analysis showed a significant association between SLE and the allele D in overall populations (odds ratio [OR] = 1.25, 95% CI: 1.07-1.48, P = 0.004). Stratification by ethnicity indicated a strong association between the allele D and SLE in Asians (OR = 1.36, 95% CI: 1.05-1.75, P = 0.019). Meta-analysis also showed a significant association between SLE and the DD genotype in overall populations (additive model) (OR = 1.38, 95% CI: 1.05-1.83, P = 0.022). In addition, we found significant associations between the recessive model and SLE in overall populations, Asians and Europeans (OR = 1.44, 95% CI: 1.11-1.88, P = 0.007; OR = 1.69, 95% CI: 1.07-2.68, P = 0.024; and OR = 1.31, 95% CI: 1.06-1.62, P = 0.013, respectively). With respect to the association between ACE I/D gene polymorphism and LN risk, there was no significant association in either the overall populations or subpopulations. The present study might suggest that ACE I/D polymorphism may be a genetic molecular marker to predict SLE, while this polymorphism may not correlate with LN susceptibility.

Associations between PTPN22 and TLR9 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis.

Previous studies have explored the relationship of PTPN22 and TLR9 polymorphisms with systemic lupus erythematosus (SLE). In consideration of the population stratification, conflicting results and updating data, we conducted a comprehensive meta-analysis, which consists of a total of 17 research articles (9120 cases and 11,724 controls) for PTPN22 and 20 articles (including up to 2808 cases and 3386 controls) for TLR9. Significant association was verified between PTPN22 rs2476601 and SLE in the overall population (OR=1.511 per T allele, 95% CI1.338-1.706, P=2.931×10-11) and under dominant model of T allele (TT+CT vs. CC: OR=1.531, 95% CI1.346-1.742, P=9.17×10-11). Analysis after stratification by ethnicity indicated that PTPN22 rs2476601 was related to SLE in Americans (OR=2.566, 95% CI 1.796-3.665, P=2.219×10-7), Europeans (OR=1.399, 95% CI 1.261-1.552, P=2.153×10-10), and Africans (OR=4.14, 95% CI 1.753-9.775, P=1.0×10-3). We did not observe any association between TLR9 polymorphisms (rs187084, rs352140, rs5743836 and rs352139) and SLE under any model, after excluding the data that were inconsistent with Hardy-Weinberg equilibrium (HWE). In summary, PTPN22 rs2476601 was significantly interrelated with SLE and contributed to susceptibility and development of SLE in Americans, Europeans and Africans in this analysis, while their relationship needs to be validated in Africans by future research.

Associations between TNFAIP3 gene polymorphisms and systemic lupus erythematosus risk: an updated meta-analysis.

In order to determine whether tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene polymorphisms confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted to examine the association between TNFAIP3 polymorphisms and susceptibility to SLE. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. A total of 23 studies from 20 articles, involving 18,501 patients with SLE and 30,435 healthy controls were included in this meta-analysis. Overall, we found significant association between SLE and the TNFAIP3 rs2230926, rs5029937, rs5029939, and rs3757173 polymorphisms (all P < 0.001). Stratification by ethnicity indicated that rs5029939 polymorphism was associated with SLE in Europeans, while rs2230926, rs5029937, and rs3757173 polymorphisms were associated with SLE both in Europeans and Asians (all P < 0.001). The results of our meta-analysis suggest that TNFAIP3 (rs2230926, rs5029937, rs5029939, and rs3757173) polymorphisms are associated with susceptibility to SLE.

Associations between the functional CD40 rs4810485 G/T polymorphism and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis.

The aim of this study was to determine whether the functional CD40 rs4810485 G/T polymorphism is associated with susceptibility to rheumatoid arthritis (RA) or with susceptibility to systemic lupus erythematosus (SLE). A series of meta-analyses were conducted to test for association between the CD40 rs4810485 G/T polymorphism and RA or SLE. A total of 21 comparisons involving 15,095 patients and 27,050 controls for RA, and 1353 patients and 2342 controls for SLE were considered. Meta-analysis showed a significant association between the CD40 rs4810485 T allele and RA in all subjects (odds ratio (OR) 0.890, 95% confidence interval (CI) 0.846-0.936, p = 5.5 × 10(-7)). After stratification by ethnicity, the CD40 T allele was found to be significantly associated with RA in Europeans (OR 0.879, 95% CI 0.848-0.901, p = 3.0 × 10(-9)). A similar pattern of association was observed between the CD40 T allele and RA when the analysis was performed using the recessive, dominant, and additive models. Meta-analysis also showed a significant association between the CD40 polymorphism and SLE in Europeans (OR for the T allele 0.715, 95% CI 0.641-0.832, p = 1.4 × 10(-6)). Our meta-analyses confirm that the CD40 rs4810485 G/T polymorphism is associated with susceptibility to RA and SLE in Europeans.

PXKlocus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility geneABHD6

To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.

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

ObjectiveThis study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE). MethodsA meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE. ResultsA 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. ConclusionsThis 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.

Fc receptor-like 3 (FCRL3) −169 C/T polymorphism and systemic lupus erythematosus: a meta-analysis

Our aim was to determine whether the Fc receptor-like 3 (FCRL3) -169 C/T (rs7528684) polymorphism confers susceptibility to systemic lupus erythematosus (SLE). A meta-analysis was conducted on the associations between the FCRL3 -169 C/T polymorphism and the SLE. A total of nine sets of comparisons containing 3,628 patients and 6,490 controls were considered. The meta-analysis showed no association between the SLE and the FCRL3 -169 C allele in all study patients (odds ratio [OR] = 0.999, 95 % confidence interval [CI] = 0.925-1.080, p = 0.986). Stratification by ethnicity indicated no association between the C allele and the SLE in neither Europeans nor Asians (OR = 1.058, 95 % CI = 0.925-1.250, p = 0.414; OR = 0.981, 95 % CI = 0.884-1.088, p = 0.715). Furthermore, analysis using the recessive model, the dominant model, and the homozygote contrast showed the same pattern for the C allele in European and Asian groups, showing no association between the FCRL3 -169 C/T polymorphism and the SLE. Even after excluding studies whose controls were not in Hardy-Weinberg equilibrium, we found that this did not materially affect the meta-analysis results. However, the single Latin American study did show an association between the FCRL3 polymorphism and the SLE under homozygote contrast (OR for CC vs. TT = 2.689, 95 % CI = 1.152-1.277, p = 0.022). This meta-analysis of published studies including 2,544 patients and 3,913 controls demonstrates that the FCRL3 -169 C/T polymorphism does not confer susceptibility to SLE in Europeans or Asians.

Association between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether the three functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518), -137 G/C (rs187238), and -1297 C/T (rs360719) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. Meta-analysis was conducted on the associations between these IL-18 polymorphisms and SLE using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 11 comparisons (nine studies) involving 8,453 subjects (2,928 SLE patients and 5,525 controls) were included in the meta-analysis. In all study subjects, meta-analysis showed no association between SLE and the IL-18 -607 C allele (odds ratio [OR] = 1.065, 95 % confidence interval [CI] = 0.870-1.303, p = 0.541). However, stratification by ethnicity indicated a significant association between this allele and SLE in Europeans (OR = 0.864, 95 % CI = 0.757-0.986, p = 0.031), but not in Asians (OR = 1.230, 95 % CI = 0.902-1.676, p = 0.190). Meta-analyses showed the same pattern for the IL-18 -607 C allele using the dominant and additive models. Meta-analysis of the IL-18 -137 G/C polymorphism showed no association between SLE and the IL-18 -137 G allele in all study subjects (OR = 0.916, 95 % CI = 0.836-1.003, p = 0.057), but stratification by ethnicity indicated a significant association between this allele and SLE in Asians (OR = 0.792, 95 % CI = 0.629-0.997, p = 0.047), but not in Europeans (OR = 0.930, 95 % CI = 0.839-1.032, p = 0.171). Furthermore, meta-analysis showed that the IL-18 -1297 C allele was significantly associated with SLE in all study subjects and in Europeans (OR = 1.240, 95 % CI = 1.052-1.482, p = 0.010 and OR = 1.303, 95 % CI = 1.050-1.617, p = 0.016). This meta-analysis shows that the IL-18 -607 C/A and -1297 C/T polymorphism are associated with the development of SLE in Europeans, and the IL-18 -137 G/C polymorphism is associated with SLE in Asians.

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

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE). 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. 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). This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.

Association between the angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether the insertion (I) /deletion (D) polymorphism within intron 16 of angiotensin-converting enzyme (ACE) confers susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN). A meta-analysis was conducted on the associations between the ACE I/D polymorphism and SLE and LN. A total of 1907 patients with SLE and 1842 controls in 18 comparative studies were included in this meta-analysis. The analysis showed a significant association between SLE and the DD genotype (recessive effect) of the ACE polymorphism (odds ratio [OR] 1.383, 95% confidence interval [CI] 1.065-1.797, p = 0.015). Stratification by ethnicity indicated a marginal association between the DD genotype and SLE in Europeans (OR 1.210, 95% CI 0.964-1.519, p = 0.099; I(2) = 0%). Meta-analysis also revealed a trend toward to an association between SLE and the ACE polymorphism using the allelic or additive models in Europeans. Furthermore, meta-analysis of the DD+ID genotype showed a significant association with LN (OR 0.582, 95% CI 0.425-0.797, p = 0.001; I(2) = 0%). This meta-analysis demonstrates a strong association between DD genotype and SLE in overall study and a marginal association between SLE and the ACE D/I polymorphism in Europeans, and suggests that this polymorphism might confer susceptibility to LN.

Associations between TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis.

The aim of this study was to determine whether the tumor necrosis factor-alpha-inducible protein 3 (TNFAIP3) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. The authors conducted meta-analyses on associations between the TNFAIP3 polymorphisms and SLE susceptibility, using fixed and random effects models. A total of eight comparative studies were included in this meta-analysis, which included four Asian, three European, and one African American population. Meta-analysis revealed that an association was found between the minor allele of rs2230926 and SLE in all subjects (odds ratio [OR] 1.848, 95% confidence interval [CI] 1.547-2.208, p<1.0×10(-9)). After stratification by ethnicity, the minor allele of rs2230926 was found to be significantly associated with SLE in Asians and Europeans (OR 1.821, 95% CI 1.495-2.219, p<1.0×10(-9); OR 2.251, 95% CI 1.830-2.768, p<1.0×10(-9)). In addition, a significant association was found between the minor allele of the rs5029939 polymorphism and the risk of developing SLE in all study subjects and Europeans (OR 1.804, 95% CI 1.255-2.592, p=0.001; OR 2.145, 95% CI 1.731-2.658, p<1.0×10(-9)). Furthermore, an association was found between the minor allele of rs3757173 and SLE in all study subjects (OR 1.540, 95% CI 1.017-2.331, p=0.041). However, no association was found between SLE susceptibility and rs6922466 (OR 0.953, 95% CI 0.812-1.120, p=0.561). This meta-analysis confirms that the TNFAIP3 polymorphisms are associated with SLE susceptibility in different ethnic groups, namely in Asians and Europeans.

Associations between TNFSF4 and TRAF1-C5 gene polymorphisms and systemic lupus erythematosus: A meta-analysis

The aim of this study was to determine whether tumor necrosis factor superfamily 4 (TNFSF4) and TNF receptor-associated factor 1-complement 5 (TRAF1-C5) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE). The authors conducted meta-analyses on associations between polymorphisms of the TNFSF4 (rs2205960, rs1234315, rs10489265) and TRAF1-C5 (rs10818488, rs3761847) genes and SLE susceptibility, using fixed and random effects models. A total of 21 comparative studies were included in this meta-analysis; meta-analysis showed an association between the minor allele of rs2205960 of TNFSF4 and SLE in all study subjects (odds ratio [OR]=1.356, 95% confidence interval [CI]=1.275-1.442, p<1.0×10(-9)). Meta-analysis revealed an association between the minor alleles of rs1234315 and rs10489265 of TNFSF4 and SLE in Asians (OR=1.366, 95% CI=1.295-1.440, p<1.0×10(-9); OR=1.463, 95% CI=1.208-1.771, p=9.7×10(-5)). The minor allele of rs10818488 of TRAF1-C5 was found to be significantly associated with SLE in Europeans (OR=1.210, 95% CI=1.115-1.313, p=5.0×10(-6)). The association p-values remained significant after multiple corrections. This meta-analysis confirms that TNFSF4 polymorphisms are associated with susceptibility to SLE in Asians and Europeans. An association was found between the rs10818488 polymorphism of TRAF1-C5 and susceptibility to SLE in Europeans.

Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether phox homology domain containing serine/threonine kinase (PXK) and tyrosine kinase 2 (TYK2) confer susceptibility to systemic lupus erythematosus (SLE). The authors conducted meta-analyses on associations between SLE susceptibility and the rs6445975 polymorphism of PXK and the rs2304256, rs12720270, rs280519, and rs1272036 polymorphisms of TYK2. A total of 13 separate comparisons studies were included in this meta-analysis. Meta-analysis identified an association between SLE and the 2 allele of the rs6445975 polymorphism in the overall population [odds ratio (OR)=1.151, 95% confidence interval (CI)=1.086-1.291, P=1.8E-06]. Stratification by ethnicity identified a significant association between this polymorphism and SLE in Europeans (OR=1.198, 95% CI=1.118-1.285, P=3.4E-07), but not in Asians. Meta-analysis identified a significant negative association between SLE and the 2 allele of the rs2304256 polymorphism in the overall population (OR=0.808, 95% CI=0.659-0.990, P=0.040), and a significant negative association was found in Europeans, but not in Asians. This meta-analysis shows that the rs6445975 polymorphism of PXK and the rs2304256 polymorphism of TYK2 are associated with the development of SLE in Europeans.

Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene

A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case-control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.