Susceptibility To Lupus Nephritis Research Articles

Peripheral CD4 +CD8 + double positive T cells: A potential marker to evaluate renal impairment susceptibility during systemic lupus erythematosus.

Lupus nephritis (LN) has a high incidence in systemic lupus erythematosus (SLE) patients, but there is a lack of sensitive predictive markers. The purpose of the study was to investigate the association between the CD4 +CD8 + double positive T (DPT) lymphocytes and LN. The study included patients with SLE without renal impairment (SLE-NRI), LN, nephritic syndrome (NS), or nephritis. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Biochemical measurements were performed with peripheral blood in accordance with the recommendations proposed by the National Center for Clinical Laboratories. The proportions of DPT cells in the LN group were significantly higher than that in the SLE-NRI group ( t=4.012, P<0.001), NS group ( t=3.240, P=0.001), and nephritis group ( t=2.57, P=0.011). In the LN group, the risk of renal impairment increased significantly in a DPT cells proportion-dependent manner. The risk of LN was 5.136 times (95% confidence interval, 2.115-12.473) higher in cases with a high proportion of DPT cells than those whose proportion of DPT cells within the normal range. These findings indicated that the proportion of DPT cells could be a potential marker to evaluate LN susceptibility, and the interference of NS and nephritis could be effectively excluded when assessing the risk of renal impairment during SLE with DPT cell proportion.

The Association between Silent Mating Type Information Regulator 2 Homolog 1 (SIRT1) Gene Polymorphism and Systemic Lupus Erythromatosis (SLE)

ABSTRACT Background Systemic lupus erythematosus (SLE) is a chronic severe multisystem autoimmune disease that affects multiple organs being characterized by heterogeneous manifestations that may affect the skin, joint, heart, brain, kidney, hematopoietic and central nervous systems. It is characterized by autoantibody production for a variety of self-antigens, but it is specifically associated with anti-double stranded DNA (anti-dsDNA), and immune complex deposition. The Silent Mating Type Information Regulator 2 Homolog 1 (SIRT1) is a NAD-dependent deacetylase enzyme that plays an important role in regulating a variety of cellular processes, such as energy metabolism, cell-cycle progression, apoptosis, aging, immune system regulation and inflammation. Aim of the Work The aim of the present study is to investigate the association of SIRT1 rs3758391 gene polymorphism with SLE and to study its impact on disease progression to lupus nephritis. Subjects and Methods This is a case control study conducted at Ain Shams University Hospital, with a total of 50 participants including 34 patients diagnosed with SLE in addition to 16 age and sex matched individuals serving as a healthy control group. Results The results revealed no significant difference between the SLE patients and the controls as regards CC, CT and TT genotypes, yet there was a statistical significant difference between both groups as regards the C and T alleles. Conclusion The present study highlights that SIRT1 gene rs3753891 does not seem to influence lupus nephritis susceptibility and disease activity as indicated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scoring. However, T allele may be a risk factor for lupus susceptibility.

Association of FCN2 gene rs3124954 and STAT4 gene rs7582694 polymorphisms with juvenile onset systemic lupus erythematosus and lupus nephritis in a sample of Egyptian children

BackgroundJuvenile onset SLE (joSLE) is multifactorial autoimmune inflammatory disease with multiple genetic liabilities. Lupus nephritis (LN) is one of the major complications of SLE. FCN2 and STAT4 gene polymorphisms are potentially linked to SLE and LN susceptibility. Aim of the workWe aimed to assess the association of FCN2 polymorphism (rs3124954) and STAT4 polymorphism (rs7582694) with risk of developing joSLE and associated LN. MethodologyOur study included 100 SLE patients, 100 LN patients and 100 matched healthy controls. FCN2 polymorphism (rs3124954) and STAT4 polymorphism (rs7582694) were genotyped using real time PCR while STAT4 protein serum levels were measured utilizing ELISA technique. ResultsThe frequency of the major C allele of FCN2 rs3124954 genotype was significantly higher while the minor T allele was significantly decreased in joSLE patients than in control subjects. The patients carrying CC genotype showed 3.7-fold elevated risk for joSLE compared to minor allele T carriers (TT and CT genotypes) under recessive model, while FCN2 rs3124954 genotypes showed no significant association with LN under any genetic model. The frequency of STAT4 rs7582694 C allele was significantly higher in joSLE patients compared to healthy subjects (p = 0.02) and in LN patients compared to joSLE only patients (p = 0.03). In LN, STAT4 rs7582694 C allele was associated with advanced stages of the disease (p = 0.02). ConclusionOur results suggested that FCN2 rs3124954 SNP minor T allele has protective tendency towards joSLE. STAT4 (rs7582694) SNP minor C allele is associated with increased risk of joSLE and its associated LN.

Association of FcγRIIA-R/H131 polymorphism and systemic lupus erythematosus lupus nephritis risk: A meta-analysis.

Previous studies have discussed association of FcγRIIA-R/H131 polymorphism and systemic lupus erythematosus (SLE), lupus nephritis (LN) risk. However, conclusions were inconsistent. A meta-analysis was performed in this study with allelic contrast (allele R vs H), additive model (genotype RR vs HH), recessive model (genotype RR vs RH + HH), and dominant model (genotype RR + RH vs HH). A total of 33 studies discussed the correlation between FcγRIIA-R/H131 polymorphism and SLE, involving 5652 SLE patients and 6322 controls. Allele R was significantly related to SLE in the overall population (odds ratio [OR]=1.238, P<.001), Asian (OR=1.237, P<.001) and European population (OR=1.212, P=.012). Additive, recessive and dominant models were correlating with SLE in the overall population (OR=1.448, P<.001; OR=1.303, P<.001; OR=1.310, P<.001), Asian population (OR=1.640, P=.001; OR=1.437, P<.001; OR=1.344, P=.005), respectively. In addition, 22 studies evaluated relation of FcγRIIA-R/H131 polymorphism with LN, involving 2065 patients with LN, and 2023 patients without LN. Results showed that allele R and the other 3 models related to LN susceptibility in the overall population when discussing differences of polymorphism between patients with/without LN. We further compared differences of polymorphism between patients with LN and controls, showing that additive and recessive models related to LN risk in the overall population, Asian, European and North American populations. In summary, FcγRIIA-R/H131 polymorphism is associated with SLE and LN.

Tumor necrosis factor gene polymorphisms are associated with systemic lupus erythematosus susceptibility or lupus nephritis in Mexican patients.

The TNF -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms have consistently been associated with systemic lupus erythematosus (SLE) in several populations; however, these findings have not been verified in all populations. Here, we aimed to examine whether the TNF -238G/A, -308G/A, -376G/A (rs1800750), and -1031T/C (rs1799964) polymorphisms confer SLE or lupus nephritis (LN) susceptibility in a Mexican population. Our study included 442 patients with SLE and 495 controls. For genotyping, we used the TaqMan 5' allele discrimination assay. The TNF -238G/A and -1031T/C polymorphisms were associated with SLE susceptibility (odds ratio (OR) 2.1, p = 0.0005 and OR 1.4, p = 0.003, respectively). Gender stratification showed a strong association between TNF -238G/A and SLE in women (OR 2.2, p = 0.00006), while TNF -1031T/C had an OR of 1.5 (p = 0.007). With regard to the TNF -376G/A polymorphism, this also showed association with SLE susceptibility (OR 1.95, p = 0.036) and LN (OR 3.5, p = 0.01). In conclusion, our study provides the first demonstration of association between the TNF -376G/A polymorphism and SLE and LN susceptibility. In addition, our study is the second documenting an association of TNF -1031T/C with SLE susceptibility. We also observed a strong association between TNF -238G/A and SLE susceptibility. The TNF 308G/A polymorphism was not associated with SLE or LN.

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.

Monocyte chemoattractant protein-1 (MCP-1)-2518 A/G polymorphism and lupus nephritis risk: A PRISMA-compliant meta-analysis.

Background:Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the development of allergic inflammatory reactions by recruiting various immune cells, which is associated with many autoimmune diseases, but the association with the MCP-1-2518A/G gene polymorphism and lupus nephritis (LN) was still controversial in previous studies. Thus, we performed a meta-analysis to derive a more precise evaluation of the association between MCP-1 -2518A/G polymorphism and LN risk and evaluated influence of ethnicity and source of controls.Methods:A systematic review and meta-analysis that will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant literatures dated to September 2016 were acquired from the PubMed, EMBASE, Cochran Library databases. A total of 961 LN cases and 1867 controls were extracted from 10 published case-control studies. We used odds ratios (OR) with 95% confidence intervals (CI) to assess the risk of LN with MCP-1-2518A/G.Results:Our meta-analysis suggested that MCP-1-2518A/G polymorphism was associated with the risk of LN (GG vs AG+AA: P < .01, OR = 1.42, 95% CI: 1.13–1.79 and A vs G P = .02, OR = 0.74, 95% CI: 0.58–0.95). Then the subgroup analysis showed MCP-1 -2518 A/G gene has a certain correlation with LN susceptibility in the American population (GG vs AA: P < .01, OR = 5.70, 95% CI: 2.09–15.50, GG vs AG+AA: P < .01, OR = 3.31, 95% CI: 1.97–5.54, GG+AG vs AA: P < .01, OR = 2.86, 95% CI: 1.14–7.18, and A vs G: P < .01, OR = 0.43, 95% CI: 0.24–0.79), while no significant risk in Europeans and Asians.Conclusion:The current meta-analysis suggests that the MCP-1-2518A/G polymorphism is associated with an increased risk of LN, especially in the American population. However, better-designed studies with larger sample sizes are needed to validate the results.

Low copy number of FCGR3B is associated with lupus nephritis in a Chinese population.

Lupus nephritis (LN) is a polygenic disease caused by an interaction between hereditary and environmental factors. Numerous gene copy number variations have been identified to contribute to this disease. Previously, immunoglobulin (Ig)G Fcγ receptor 3B (FCGR3B) copy number variation (CNV) was reported to be associated with LN in the Caucasian population. However, the effect of FCGR3B CNV on LN in the Chinese population remains unknown. The present study aimed to investigate whether CNVs of FCGR3B are associated with LN in the Henan Chinese population. FCGR3B CNVs were determined in 142 LN patients and 328 healthy controls. A modified methodology based on competitive polymerase chain reaction, a Multiplex AccuCopy™ kit was used to detect FCGR3B copy number. Clinical and laboratory data was collected retrospectively from medical records. To evaluate associations between FCGR3B CNVs and LN susceptibility, the present study calculated the odds ratios using a logistic regression analysis. The current study identified that the distribution of FCGR3B copy number was significantly different between LN and healthy controls (P=0.031). A low copy number (<2) of FCGR3B was significantly enriched in LN patients (P=0.042), and was a risk factor for LN (odds ratio=2.059; 95% confidence interval, 1.081-3.921; P=0.028). However, a high copy number (>2) had no effect on LN. There were no associations between FCGR3B CNV and clinical phenotypes of LN. The results from the present study demonstrate that a low copy number of FCGR3B is a risk factor for LN in a Chinese population.

Genetics of human lupus nephritis

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by immune complex formation with multi-organ manifestations. Lupus nephritis (LN) is one of the most severe types of organ damage in SLE, and it clearly contributes to increased morbidity and mortality due to SLE. LN occurs more frequently and is more severe in non-European ancestral backgrounds, although the cause of this disparity remains largely unknown. Genetic factors play an important role in the pathogenesis of SLE. Although many SLE susceptibility genes have been identified, the genetic basis of LN is not as well understood. While some of the established general SLE susceptibility genes are associated with LN, recent discoveries highlight a number of genes with renal functions that are specifically associated with LN. Some of these genes associated with LN help to explain the disparity in the prevalence of nephritis between individuals with SLE, and also partially explain differences in LN between ancestral backgrounds. Moreover, not only the gene mutations, but also post-translational modifications seem to play important roles in the pathogenesis of LN. Overall it seems likely that a combination of general SLE susceptibility genes cooperate with LN specific risk genes to result in the genetic propensity for LN. In this review, we will outline the genetic contribution to LN and describe possible roles of LN susceptibility genes.

Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the FCGR2B-FCRLA Locus.

Cyclophosphamide (CYC) is an immunosuppressant drug widely used to treat various diseases including lupus nephritis, but its efficacy highly varies from individual to individual. This pharmacogenomics association study searched for genetic variations associated with CYC efficacy. Genome-wide association scan was performed for 109 Korean patients with systemic lupus erythematosus with lupus nephritis (classes III-V) who received intravenous CYC induction therapy. Genetic differences between responders and nonresponders were examined using Cochran-Armitage trend tests, and genotype imputation was used for defining the association locus. Genetic polymorphisms in the Fcγ receptor gene (FCGR) cluster at human chromosome 1q23, previously associated with lupus nephritis susceptibility, were associated with the response to CYC treatment for lupus nephritis. Significant response association was found for 3 perfectly correlated (r(2) = 1) single-nucleotide polymorphisms (SNP): rs6697139, rs10917686, and rs10917688, located between the FCGR2B and FCRLA genes (p = 3.4 × 10(-8)). Carriage of the minor alleles in these SNP was found only in nonresponders (31%) and none in responders (0%). This first genome-wide association approach for CYC response yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to CYC metabolism and efficacy.

IL10 in Lupus Nephritis: Detection and relationship with disease activity.

IntroductionGlomerulonephritis is a major determinant of the course and prognosis of systemic lupus erythematosus (SLE) and is evident in 40%–85% of patients. IL10, a cytokine produced by monocytes and-to a lesser extent-lymphocytes, has pleiotropic effects in immune regulation and inflammation. It enhances B cell survival, proliferation, differentiation, and antibody production; these effects play a role in autoimmune diseases. Among identified polymorphisms in the IL10 promoter, three linked single nucleotide polymorphisms (SNPs) of −1082 G/A, 819 T/C, and −592 A/C have been shown to influence the IL10 gene expression. Compared with the −592 C allele, the 592 A is associated with lower IL10 production in vitro. The objectives of this study were to investigate the −592 A/C polymorphism in patients with and without lupus nephritis and to assess its influence on IL10 secretion in vivo and its role in pathogenesis and clinicopathological characteristics of lupus nephritis.MethodsThis case control study was conducted on 40 SLE patients recruited for the study from those attending the nephrology department of the Theodor Bilharz Research Institute (outpatient clinic and inpatient ward) in 2013. Patients were divided into two groups, group I (SLE patients without evidence of nephritis) and group II (SLE patients with lupus nephritis). Data were analyzed using SPSS (version 12), a t-test, Chi square, ANOVA, and the Pearson product–moment correlation coefficient.ResultsOur study found an increase in IL10 serum in lupus nephritis patients compared to those without renal involvement (without statistical significance). No significant differences emerged in the level of IL10 serum among different pathological classes.ConclusionThe IL10 gene (−592 A/C) polymorphism, though not associated with lupus nephritis’s susceptibility in the present study, does play a role.

Evaluating the association of interleukin-10 gene promoter -592 A/C polymorphism with lupus nephritis susceptibility

BackgroundInterleukin-10 (IL-10) is an important immunoregulatory cytokine. There are few studies evaluating the association between IL-10 and lupus nephritis (LN). The aim of this study was to evaluate the association of IL-10 gene promoter -592 A/C with LN susceptibility. MethodsThe study was conducted on 84 patients with systemic lupus erythematosus (SLE). Patients were divided into LN group (Group I, 48 patients) and non-LN group (Group II, 36 patients). The -592 A/C polymorphisms in IL-10 promoter gene were determined by polymerase chain reaction and restriction fragment length polymorphism in both groups. IL-10 was determined by enzyme-linked immunosorbent assay. Frequencies of the genotypes were compared between LN and non-LN patients and among LN patients with different pathologic classes. ResultsThere was a significant increase in serum level of IL-10 (P = 0.001) in Group I compared with Group II and significant positive correlation between serum IL-10 and SLE disease activity index (r = 0.466, P = 0.001) in Group I. There were no significant differences in the distribution of the IL-10 gene promoter -592 A/C genotypes or the allele frequencies between Groups I and II. There was no significant difference between AC/CC and AA genotypes with SLE disease activity index, proteinuria, hematuria, anti-double-stranded DNA, and IL-10 in Group I. There was no significant difference in the distribution of AC and CC genotypes among different pathologic LN classes. ConclusionIL-10 suggested to play a role in pathogenesis and development of LN. However, the promoter -592 A/C of IL-10 gene suggested to be not associated with serum IL-10 levels or LN susceptibility. In addition, it appears that promoter -592 A/C of IL-10 gene not associated with LN activity or the pathologic classes of LN.

Angiotensin-converting enzyme gene polymorphism in Thai patients with systemic lupus erythematosus.

To determine the association between angiotensin-converting enzyme (ACE) I/D polymorphism and the presence of systemic lupus erythematosus (SLE) disease and lupus nephritis (LN), including the association with disease severity in a Thai population. In this retrospective study, 187 SLE patients followed up for (at least) 7years in a rheumatology clinic of an academic hospital were enrolled. Disease severity and damage score at diagnosis and every 6months, including treatment outcome of the first episode of LN were retrieved from medical records. The ACE genotype of SLE patients were determined by polymerase chain reaction and compared with ACE genotype in 687 controls from a database of a Thai surveillance cohort. There was an association between ACE I/D polymorphism and the presence of SLE disease and LN (P<0.001). Unexpectedly, the prevalence of DD genotype in SLE patients was lower than controls (OR 0.44 [95% CI 0.23-0.84], P=0.013). The prevalence of ID genotype was not different between SLE patients and controls (OR 1.44 [95%CI 0.93-2.24], P=0.102), but was higher in LN patients compared to controls (OR 1.77 [95% CI 1.14-2.72], P=0.01). However, the ACE I/D polymorphism is not associated with SLE disease severity, either in patients with or without nephritis. The DD genotype could not be used as a poor prognostic marker for SLE and LN susceptibility in a Thai population. However, ID genotype may be associated with risk to develop LN.

APO-1/FAS Promoter (-670A/G) Polymorphisms and Risk of Lupus Nephritis in SLE Egyptian Female Patients

Background: Self-immunization in systemic lupus is driven by defective in apoptosis. Fas, is an apoptosis-promoting cell surface receptor. The present study evaluate the possible association between APO-1/FAS Promoter (-670A/G) Polymorphism and sFAS level with susceptibility to lupus nephritis in SLE patients. Design and Methods: This study was performed on 88 female patients with SLE (mean age, 39.82 ± 10.16 years). 82 patients with lupus nephritis (mean age, 42.50 ± 6.65 years). 150 age and sex-matched person served as controls. All participants were genotyped for the APO-1/FAS Promoter (-670A/G) Polymorphism, manifestations and serum sFAS were correlated with the genotypes. Results: Serum sFAS was significantly higher in patients with -670 AA genotype compared to others. (-670A/G) AA genotype frequencies were significantly higher in the lupus nephritis and SLE patients groups compared with the controls and were associated with increased risk for lupus nephritis and SLE development (odds ratio, 4.08 and 1.91 respectively). Conclusions: The APO-1/FAS Promoter (-670A/G) A allele can be used as a genetic marker for lupus nephritis susceptibility in SLE and was associated with high sFAS level.

Relationship between chemokine receptor 5 Δ32/W gene polymorphism and lupus nephritis

Results from the published studies on the association between chemokine receptor 5 (CCR5) Δ32/W gene polymorphism and lupus nephritis (LN) are still conflicting. This meta-analysis was performed to evaluate the relationship between CCR5 Δ32/W gene polymorphism and LN and to explore whether CCR5 Δ32 allele, Δ32/Δ32 and W/W genotypes could become a predictive marker for systemic lupus erythematosus (SLE) developing into LN. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of March 1, 2014, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Five investigations were identified for the analysis of association between CCR5 Δ32/W gene polymorphism and LN. In the overall populations, Asians, Caucasian population, the association between CCR5 Δ32/W gene polymorphism and LN susceptibility was not found. Interestingly, a trend toward an association of Δ32 allele and W/W genotype with LN risk was observed in African population. However, this meta-analysis only included one study for the study in Africans. We also found that the gene distribution of CCR5 Δ32/W gene polymorphism between SLE group and LN group were not different. In conclusion, our results indicate that CCR5 Δ32/W gene polymorphism was not associated with LN risk and might be no a significant genetic molecular marker to predict the SLE patients developing into LN. However, more investigations are required to further clarify this association.

Lupus Nephritis Susceptibility Loci in Women with Systemic Lupus Erythematosus

Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci.

Chemokine receptor 5 (CCR5) delta 32 polymorphism in lupus nephritis: A large case-control study and meta-analysis

Objectives: Recent animal experiments showed that CCR5-deficient lupus mice (CCR5−/−) were closely associated with aggravated lupus nephritis. CCR5 Δ32 variation, a nonsynonymous mutation of CCR5, resulted in altered CCR5 function. However, the CCR5 Δ32 mutation in human lupus nephritis has been rarely reported in the literature. Methods: A large case-control study that included 2010 samples from a Chinese population was conducted, followed by a meta-analysis combining the current and previously published studies to explore the effect of CCR5 Δ32 on lupus nephritis susceptibility. Results: Four CCR5 Δ32 heterozygote carriers were detected in lupus nephritis patients only. We detected no CCR5 Δ32 homozygotes in our study population. In the meta-analysis, including 1,092 cases and 2,229 controls, we found great heterogeneity between studies (p < 0.001, I2 = 89.6%). Furthermore, stratified and sensitivity analyses suggested that ethnicity and CCR5 Δ32 allele frequency were the main origin of heterogeneity. In the subgroups without obvious heterogeneity, we observed a positive correlation between CCR5 Δ32 and lupus nephritis risk (p < 0.05). Conclusions: Our study confirmed that the CCR5 Δ32 mutation is a very rare variation found in the Chinese population with Han ethnicity. However, CCR5 Δ32 might play a role in lupus nephritis susceptibility. Future replications and functional studies are needed.

Retracted Association of STAT4 gene polymorphism with systemic lupus erythematosus / lupus nephritis risk.

The association of STAT4 gene polymorphism with systemic lupus erythematosus (SLE) / lupus nephritis (LN) results from the published studies is still conflicting. This meta-analysis was performed to evaluate the relationship between STAT4 rs7574865, rs16833431, rs11889341, rs8179673, rs10168266, rs7582694, rs3821236, rs7601754 gene polymorphism and SLE / LN, and to explore whether STAT4 gene polymorphism could become a predictive marker for SLE / LN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2013, and eligible investigations were synthesized using meta-analysis method. 24 investigations were identified for the analysis of association between STAT4 gene polymorphism and SLE, consisting of 31190 patients with SLE and 43940 controls. In STAT4 rs7574865, there was a marked association between T allele or TT genotype and SLE susceptibility (T: OR=1.53, 95% CI: 1.30-1.79, P<0.00001; TT: OR=1.60, 95% CI: 1.34-1.92, P<0.00001), and GG homozygous was associated with SLE risk (OR=0.62, 95% CI: 0.51-0.75, P<0.00001). Furthermore, rs8179673, rs7582694, or rs3821236 minor allele frequency was associated with the risk of SLE, but this association was not found in rs16833431, rs11889341, rs10168266, rs7601754, however, the number of included studies was small and the results were less robust. In addition, STAT4 rs7574865 gene polymorphism was not associated with the LN risk. Our results indicate that T allele or TT homozygous is a significant risk genetic molecular marker to predict the SLE susceptibility and GG genotype is a valuable marker to against the SLE risk, but the association was not found for LN. However, more investigations are required to further clarify the association of the T allele or TT homozygous with SLE / LN susceptibility.

Do Asian patients have worse lupus?

The predisposition to and clinical phenotype of systemic lupus erythematosus, an autoimmune disease that is associated with significant morbidity and mortality, are affected by genetic and environmental factors. This article aims to examine whether Asians have worse lupus by reviewing the literature on genetic predisposition and clinical outcomes, including major organ involvement, damage score and mortality in Asian populations compared with other ethnicities. A number of lupus nephritis susceptibility genes have been identified in Asians and White patients, with further variations among different Asian populations. Meta-analysis studies on various Fcγ receptor subtypes revealed that FcγRIIIA-F158 allele, which is associated with low binding affinity to IgG1 and IgG3, predisposed to lupus nephritis in Asian patients. Asian patients were reported to have higher rates of lupus nephritis-associated autoantibodies, lupus nephritis and more active glomerulonephritis compared with White patients. Renal outcome and the level of immunosuppressant use in Asians were comparable to Afro-American Blacks in some studies. Asians were also found to have higher overall damage scores compared with Whites. The difference in mortality between Asian patients and other ethnicities in different geographical regions was found to vary depending on socioeconomic factors such as access to health care. Poverty, education level, cultural and behavioural factors are confounders to ethnicity in determining clinical outcome of systemic lupus erythematosus.

Fcγ receptor IIB and IIIB polymorphisms and susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis

The aim of this study was to explore whether polymorphisms of the Fcgamma receptors (FcgammaRs) IIB T/I232 and FcgammaRIIIB NA1/NA2, confer susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN). The authors conducted a meta-analysis on associations between the FcgammaRIIB T/I232 and FcgammaRIIIB NA1/NA2 polymorphisms and SLE and LN susceptibility as determined using 1) allele contrast, 2) recessive, 3) dominant models and 4) contrast of homozygotes. A total of 16 separate comparisons were considered, consisting of 2887 SLE patients and 3105 controls. Meta-analysis of the FcgammaRIIB T/I232 polymorphism showed a significant association between the FcgammaRIIB T allele and the risk of developing SLE compared with the FcgammaRIIB I allele (OR = 1.207, 95% CI = 1.061-1.373, P = 0.004). In subjects of Asian descent, a significant association was observed between the FcgammaRIIB T allele and SLE (OR = 1.332, 95% CI 1.138-1.558, P < 0.001). However, in Europeans no such association was found. In contrast, no association was found between SLE or LN and the FcgammaRIIIB NA1/NA2 polymorphism in all subjects, or in European and Asian populations. This meta-analysis shows that the FcgammaRIIB T/I232 polymorphism confers susceptibility to SLE, especially in Asian-derived populations.