Systemic Lupus Erythematosus In Chinese Research Articles

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Missense polymorphisms within IL-10R1 exons are not associated with systemic lupus erythematosus in Chinese

Studies have suggested that interleukin-10 receptor1 (IL-10R1) is involved in genetic susceptibility to systemic lupus erythematosus (SLE) in animal models and Caucasians. Therefore, the current study was designed to determine whether the IL-10R1 gene plays a role in the pathogenesis of human SLE in the Chinese Han population. The seven exons of the IL-10R1 gene were amplified and sequenced using a BigDye Terminator v1.1 Cycle Sequencing kit and an ABI 3100 DNA Analyzer. A missense single nucleotide polymorphism (SNP) locus with a minor allele frequency of at least 0.1 was chosen to evaluate the correlation with the incidence of SLE. Seven SNPs were found to reside in the exons of the IL-10R1 gene. Among the SNPs, A744G was evaluated for a correlation with the incidence of SLE because A744G was the only missense SNP with a minor allele frequency of at least 0.1. There was no significant difference in the distribution of the A and G alleles between the SLE patient group and the healthy control group (P = 0.693). Furthermore, the genotype frequencies of A744A, A744G and G744G did not differ significantly between the two groups (P = 0.906). In the Chinese Han population, missense SNPs within the exons of the IL-10R1 gene do not contribute to the development of SLE.

Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 × 10−9; TNFSF4, rs844648, OR=1.22, P=2.47 × 10−3; TNFSF4, rs2205960, OR=1.30, P=2.41 × 10−4). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 × 10−3). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 × 10−8, respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 × 10−3), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.

Management of systemic lupus erythematosus in Chinese patients

Systemic lupus erythematosus (SLE) is a worldwide disease with prevalence figures ranging from nine to 130 per 100,000 individuals. SLE appears to be more prevalent in certain ethnic groups, such as the African–Americans, African–Caribbeans and Asians. The prevalence of SLE in Hong Kong Chinese was estimated to be 59 out of 100,000 (104/100,000 among women), which is mid-way between that of the Caucasians and African–Americans. Certain organ manifestations, such as lupus nephritis, are more common in Chinese than Caucasians. A recent prospective study reported that the cumulative incidence of renal disease within 5 years of diagnosis of SLE in Chinese patients was 60%. Despite the improvement in survival of SLE in the past few decades, manifestations that are refractory to conventional therapies and treatment related complications are still major challenges in the management of SLE. Novel-therapeutic modalities for SLE should aim at targeting more specifically the immunopathogenetic pathways to achieve higher efficacy and reduce short- and long-term therapy-related toxicities. This review summarizes the management strategies and novel therapeutic modalities in SLE.

Osteopontin Gene Polymorphism and Systemic Lupus Erythematosus in Chinese

Osteopontin Gene Polymorphism and Systemic Lupus Erythematosus in Chinese

Polymorphisms of the toll-like receptor 9 (TLR9) gene with systemic lupus erythematosus in Chinese

Polymorphisms of the toll-like receptor 9 (TLR9) gene with systemic lupus erythematosus in Chinese

Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus.

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

Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations.

The association of Fcgamma receptor (FcgammaR) polymorphisms with systemic lupus erythematosus (SLE) has been demonstrated in various populations; however, the results have been inconsistent. We recently identified a single-nucleotide polymorphism encoding a non-synonymous substitution, Ile232Thr (I232T), of FCGR2B and its association with SLE in Japanese and in Thais. Multiple functional FcgammaR genes with polymorphisms (FCGR2A, FCGR2B, FCGR3A, and FCGR3B) cluster in 1q23, and some of them are in linkage disequilibrium (LD). To differentiate contributions from multiple-linked loci, comparison of different populations may provide useful information. In this study, we analyzed the above four FCGR polymorphisms of the Chinese patients and controls for the association with SLE. FCGR2A-H131R, FCGR2B-I232T, FCGR3A-F176V, and FCGR3B genotypes were determined in 167 Chinese patients with SLE and 129 healthy controls. Association was examined using case-control analysis. Allele frequencies of FCGR2B-232T and FCGR3A-176F were significantly increased in SLE [odds ratio (OR) = 1.67 and OR = 1.41, respectively]. Interestingly, while these alleles had a tendency of positive LD in the controls, FCGR2B-232T was in positive association with FCGR3A-176V in SLE, suggesting that these two alleles were associated with SLE in an independent manner. Comparison between SLE with and without nephritis indicated significant association of FCGR2B-232T with nephritis (OR = 2.65). When the present results were combined with our previous data on the Japanese and the Thais using meta-analytic methods, highly significant and independent association was observed for FCGR2B and FCGR3A genotypes. These results strongly suggested that FCGR2B is a common susceptibility factor to SLE in the Asians.

HLA and systemic lupus erythematosus in Chinese

Seventy-five unrelated Chinese SLE patients were HLA typed and subdivided into mild and severe disease The HLA-B13 was associated with mild disease Fourteen of 30 (46.7%) mild disease patients had B13 compared to 63/330 (19.1%) normal subjects ( p < 0 0005, corrected p < 0 013, RR = 3 7) The HLA-B17 on the other hand was observed in 29% of 45 severe disease patients compared to 13 9% of 330 normal subjects ( p < 0 01, RR = 2.5). The frequency of HLA-B17 in 11 patients who died was even higher (45 5%).