Association of mtDNA M/N haplogroups with systemic lupus erythematosus: a case-control study of Han Chinese women.
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ABSTRACT:
SUBMITTER: Tang Y
PROVIDER: S-EPMC4454022 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Background. Systemic lupus erythematosus (SLE) is a complex immune disease. The genetic variation in the IL-12b gene was found to associate with SLE in Caucasian population. In this study, we examined this association in Chinese Han population by a recently developed method, unlabeled probe-based high resolution melting analysis. Methods. A total of 297 SLE patients and 351 controls were recruited. Unlabeled probe-based high resolution melting analysis (HRMA) was used in genotyping. Results. Statistically significant differences were observed in both genotype and allele frequencies for rs6887695 in the SLE patients as compared with the controls. Minor allele (C) of rs6887695 (P = 0.031, OR 0.78, [95% CI 0.63-0.98]) was found to be protective against SLE. The association of SNP rs6887695 with the diagnostic criteria of SLE was also examined. Minor allele (C) exerts protective effect on the incidence of arthritis (P = 0.013, OR = 0.65, 95% CI = 0.47-0.92) and abnormalities of antinuclear antibody (P = 0.022, OR = 0.68, 95% CI = 0.49-0.95). IL-12b SNPs were irrelevant to other diagnostic criteria of SLE. Summary. Polymorphisms of rs6887695 in IL-12b gene were associated with disease risk, as well as arthritis and antinuclear antibody synthesis, of systemic lupus erythematosus in Chinese population.
| S-EPMC3362034 | biostudies-literature
Project description:Objective To investigate the association of the CD11b single nucleotide polymorphism (SNP) rs1143679 with systemic lupus erythematosus (SLE) in Han Chinese patients, and to clarify this association with SLE clinical manifestations. Methods PCR-restriction fragment length polymorphism and direct sequencing of CD11b rs1143679 were conducted in 584 patients with SLE and 628 healthy controls in this case-control study to compare genotype and allele frequency distributions. Correlations between CD11b genotypes and clinical manifestations were also determined. Results The frequency of the CD11b rs1143679 GA genotype was 1.89% in Han Chinese patients with SLE, which was much lower than that of European and American populations, but close to the frequency observed in individuals from Hong Kong and Thailand. The CD11b rs1143679 GA genotype was also shown to confer susceptibility to SLE (odds ratio?=?4.00, 95% confidence interval?=?1.11-14.41). CD11b rs1143679 was found to be significantly associated with nephritis, but not with age of disease onset, arthritis, hematological involvement, or neural lesions. Conclusion CD11b rs1143679 appears to be associated with risk for SLE in the Han Chinese population, and may play an important role in the development of lupus nephritis.
| S-EPMC5972232 | biostudies-literature
Project description:IntroductionSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Currently, numerous genetic loci of SLE have been confirmed. Here we try to further explore additional genes contributing to SLE susceptibility in this study.MethodsForty nine single nucleotide polymorphisms (SNPs) with moderate-risk for SLE in previous study were genotyped in a large-scale replication study with a total of 3,522 cases and 8,252 controls using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate through PLINK 1.07 software.ResultsThis replication effort confirmed five reported SLE susceptibility loci reaching genome-wide levels of significance (P(meta) <5.00 × 10(-08)): TNFSF4 (rs1418190, odds ratio (OR) = 0.81, P(meta) = 1.08 × 10(-08); rs4916219, OR = 0.80, P(meta )= 7.77 × 10(-09)), IRF8 (rs2934498, OR = 1.25, P(meta) = 4.97 × 10(-09)), miR-146a (rs2431697, OR = 0.69, P(meta) = 1.15 × 10(-22)), CD44 (rs2732547, OR = 0.82, P(meta) = 1.55 × 10(-11)), and TMEM39A (rs12494314, OR = 0.84, P(meta) = 1.01 × 10(-09)). Further logistic regression analysis indicated that the genetic effects within TNFSF4 detected in this study are independent from our previously reported signals.ConclusionsThis study increases the number of established susceptibility loci for SLE in Han Chinese population and highlights the contribution of multiple variants of modest effect. Although further studies will be required to identify the causal alleles within these loci, the findings make a significant step forward in our understanding of the genetic contribution to SLE in Chinese population.
| S-EPMC4404072 | biostudies-literature
Project description:This study aimed to assess the association between 14 single nucleotide polymorphisms (SNPs) in six genes (IRF8, TMEM39A, IKZF3, ORMDL3, GSDMB, and ZPBP2) and systemic lupus erythematosus (SLE) in a Chinese Han population sample.We carried out a case-control study of 415 patients with SLE and 470 healthy controls without autoimmune disease or cancer. DNA for genetic analysis was isolated from the blood of all subjects using standard phenol-chloroform method. TagSNPs were identified using genotype data from the panel (Han Chinese in Beijing) of the HapMap Project and were selected using the Haploview program. Genotyping assay was conducted using the Sequenom MassARRAY iPLEX Gold platform. The frequencies of the alleles and genotypes were calculated and analyzed. Association studies and haplotype analysis were also performed.The genotypic frequencies of rs12493175 and rs13062955 were significantly different between the SLE patients and the healthy controls. Compared with the common homozygous genotype, the CT and CT?+?TT genotypes in rs12493175 and the AC and AC?+?AA genotypes in rs13062955 was observed to significantly reduce the risk of SLE. The haplotype analysis of TMEM39A polymorphisms showed that the CGTA haplotype frequency was significantly low in the SLE patients.Our findings identified three novel associations in SNPs located in the TMEM39A gene associated with SLE susceptibility in a Chinese Han population.
| S-EPMC5399404 | biostudies-literature
Project description:ObjectiveIt has been reported that IKAROS family of zinc finger 3 (IKZF3)-deficient mice spontaneously develop human systemic lupus erythematosus (SLE)-like phenotypes and produce anti-dsDNA Ab leading to immune complex-mediated glomerulonephritis. Polymorphism of the IKZF3 gene corresponds with the susceptibility to several immune-related diseases. Our intention was to establish an association between polymorphisms in the IKZF3 gene and SLE in the Chinese Han population.MethodsThe study involved obtaining blood samples for DNA extraction and genotyping the 4 selected single-nucleotide polymorphisms (SNPs) in IKZF3, including rs12150079, rs9909593, rs907091, and rs2872507, by performing PCR restriction fragment length polymorphism analysis (PCR-RFLP). A group of 366 SLE patients were compared to 455 healthy controls.ResultsA significant decrease in frequencies of the rs907091 CC genotype and C allele appeared in the SLE patients unlike that observed in the controls (p = 0.001 and 0.015, respectively). The frequencies of the rs12150079 genotype and allele were different between the SLE patients and the control individuals, although the significance was only marginal (p = 0.046 and 0.049, respectively). In addition, a significantly low frequency of the GGCG haplotype was observed in the SLE patients, suggesting that it may provide protection against SLE (p = 0.011).ConclusionTo the best of our knowledge, this is the first study to demonstrate an important association between polymorphisms in IKZF3 and SLE in the Chinese Han population. A strong association between rs907091 in the IKZF3 gene and SLE was identified.
| S-EPMC4182708 | biostudies-literature
Project description:In a previous study, we have reported an increased plasma midkine (MK) and pleiotrophin (PTN) concentrations in patients with systemic lupus erythematosus (SLE) and the increase in MK and PTN associated with inflammatory cytokines interleukin (IL)-17 level and some clinical manifestations, suggesting the underlying association of MK and PTN with SLE. This study was conducted to investigate the association between common single-nucleotide polymorphisms (SNPs) in the MK and PTN gene and SLE susceptibility. A total of 989 subjects (496 SLE patients and 493 healthy controls) were included and genotyped for three MK SNPs and seven PTN SNPs in using improved multiple ligase detection reaction (iMLDR). Results have demonstrated no significant differences for genotype and allele frequencies in all 10 SNPs between SLE patients and healthy controls. Case-only analysis in SLE revealed that, in MK gene, the genotype frequency of AA/AG (rs35324223) was significantly lower in patients with photosensitivity than those without; the allele frequency of A/G (rs20542) was significantly higher in patients without serositis. In PTN gene, the A/G allele frequency (rs322236), C/T allele frequency, and TT/CT genotype frequency (rs6970141) showed significantly increased results in patients with immunological disorder compared to those without. Furthermore, no significant differences in plasma MK and PTN concentrations with its SNPs genotypes were found. MK and PTN SNPs showed no associations with SLE genetic susceptibility, but it may be associated with the course of this disease; further studies are needed to focus on the mechanism of MK and PTN genes in the pathogenesis of SLE.
| S-EPMC7046794 | biostudies-literature
Project description:ObjectiveThe gene SLC15A4 (solute carrier family 15 [oligopeptide transporter], member 4) has been reported as contributing to the pathogenesis of systemic lupus erythematosus (SLE). We performed a case-control replication study to investigate further the association between single-nucleotide polymorphisms (SNPs) in the SLC15A4 gene and systemic SLE in a Han Chinese population.MethodsIn Han Chinese SLE patients and healthy individuals (n = 355, 375, respectively), 18 SNPs in the SLC15A4 gene were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and TaqMan SNP genotyping assays. Analyses of allele frequencies and genotypes using codominant, dominant, and recessive models were conducted, as well as a linkage disequilibrium analysis. P values < 0.05 were considered significant.ResultsAllele frequencies of five of the analyzed SNPs were significantly associated with SLE. Under a codominant model the genotype frequencies of rs3765108 AG and rs7308691 AT were significantly higher in the SLE group than the control group (p = 0.019, 0.049, respectively). Under a dominant model the rs1385374 (TT+CT) SNP carried a higher risk of SLE than (CC) (p = 0.042). One SLC15A4 haplotype (TA), which consists of 2 SNPs (rs959989 and rs983492), was associated with SLE (p = 0.024).ConclusionOur study determined that five SNPs (rs959989, rs1385374, rs983492, rs12298615, and rs10847697) are associated with SLE. Thus, SLC15A4 may be important in the pathogenesis of SLE in Han Chinese patients.
| S-EPMC4991581 | biostudies-literature
Project description:BackgroundSystemic lupus erythematosus (SLE) affects many organs and systems of the human organism, at present, its specific pathogenesis is not completely clear, but inflammation is considered to be an important factor involved in the pathogenesis and progression of SLE. Gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL) have different effects on inflammation: GGT has pro-inflammatory effects, on the contrary, TBIL has anti-inflammatory effects. Study has found that GGT and TBIL play opposite roles in metabolic diseases. However, the roles of them in SLE are unknown. Meanwhile, the relationship between GGT and SLE also remains unexplored.MethodWe recruited 341 SLE patients and 332 healthy individuals in Liaocheng People's Hospital from August 2018 to May 2019. We diagnosed SLE using 2019 revised American College of Rheumatology (ACR) SLE criteria, and modeled the study outcomes using logistic regression to explore the respective relationship between GGT, TBIL and SLE. We also analyzed the interaction of GGT and TBIL in the progression of SLE.ResultsWe found that the levels of CRP, IL-6 and TNF-α in the aggravated group were significantly higher than those in the unaggravated group, the levels of C3 and C4 in the aggravated group were significantly lower than those in the unaggravated group. According to Spearman correlation analysis, GGT is proportional to CRP (rs=0.417) and IL-6 (rs=0.412), inversely proportional to C3 (rs=-0.177) and C4 (rs=0.-132). TBIL was inversely proportional to CRP (rs=-0.328) and TNF(rs=-0.360), and positively proportional to C3 (rs=0.174) and C4 (rs=0.172). In the fully adjusted model, compared to the lowest quartile, the highest quartile of GGT exhibited a positive association with the risk of SLE aggravation (OR=2.99, 95% CI: 1.42-6.31, P<0.001). At the same time, compared to the highest quartile, the quartile lowest of TBIL exhibited a positive association with the risk of SLE aggravation (OR=2.66, 95% CI: 1.27-5.59, P<0.001) in the fully adjusted model. Through interaction analysis, we found that women with high GGT levels had an increased risk of SLE aggravation when they had a low level of TBIL (OR=3.68, 95% CI: 1.51-9.01, for women with Q1 TBIL and Q4 GGT compared to women with Q2-Q4 TBIL and Q1-Q3 GGT, P for interaction <0.001), the combined AUC value (AUCCOMBINED=0.711) of high GGT level and TBIL were higher than their respective values (AUCGGT=0.612, AUCTBIL=0.614).ConclusionWe found that the effects of GGT and TBIL in the progression of SLE are opposite. High GGT level might be a risk factor for SLE aggravation, as GGT levels increased, so did the risk of SLE aggravation. At the same time, we found that low TBIL level might be a risk factor for SLE aggravation. Moreover, high GGT level and low TBIL level had a subadditive effect on the increased risk of SLE aggravation.
| S-EPMC8277571 | biostudies-literature
Project description:TBX21 recode T-bet which is an important transcription factor that drives the Th1 immune response primarily by promoting expression of the interferon-gamma (IFNG) gene. Recent studies have shown that genetic variants in TBX21 and IFNG are connected with risk of systemic lupus erythematosus (SLE). The aim of the present study was to replicate these genetic associations with SLE in Anhui Chinese population. Genotyping of 3 variants (rs4794067 in TBX21, rs2069705 and rs2069718 in IFNG) was performed. A total of 3732 subjects were included in the final analysis. The study only identified the association of rs2069705 with SLE susceptibility (T vs. C: odds ratio [OR]?= 1.12, 95% confidence interval [CI]?= 1.00-1.26, P = 0.046). Combined analysis with Hong Kong GWAS showed that the OR for rs2069705 was 1.10 (95% CI: 1.01-1.21, P = 0.027). Further pooled analysis with Korean populations involving 10498 subjects showed a more significant association between rs2069705 and SLE (T vs. C: OR = 1.11, 95%CI = 1.04-1.19, P = 0.002; TT + TC vs. CC: OR = 1.11, 95%CI = 1.02-1.21, P = 0.012; TT vs. TC + CC: OR = 1.28, 95%CI = 1.07-1.54, P = 0.008; TT vs. CC: OR =? .33, 95%CI = 1.10-1.60, P = 0.003). In addition, we also identified a significant genetic interaction between rs2069705 and rs4794067 in Anhui Chinese population. Our study suggests that IFNG and IFNG-TBX21 interaction are involved in SLE susceptibility.
| S-EPMC4768161 | biostudies-literature
Project description:Interleukin-35 (IL-35) exerts crucial roles in the pathogenesis and development of systemic lupus erythematosus (SLE), in this study we aim to explore the associations between IL-35 gene polymorphisms and the susceptibility, clinical features and plasma IL-35 levels of SLE patients, respectively. 490 SLE patients and 489 healthy controls were recruited in our study. The correlations between the polymorphisms of seven SNPs of IL-35 encoding gene and the susceptibility, main clinical manifestations of SLE were evaluated, respectively. Plasma IL-35 levels were assessed in 76 SLE patients, and the associations between plasma IL-35 levels and the polymorphisms of genotyped SNPs were explored. There were significant associations between the polymorphisms of rs4740 and the occurrence of renal disorder, hematological disorder in SLE patients, respectively (p = 0.001; p = 0.001). In addition, there were no significant associations observed between the genotype frequencies of genotyped SNPs and the risk of SLE, plasma IL-35 levels, respectively. The polymorphism of rs4740 of IL-35 encoding gene is associated with the occurrence of renal disorder and hematological disorder of SLE patients.
| S-EPMC6523873 | biostudies-literature