Association Study of IFIH1 rs1990760 Polymorphism with Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a complex autoimmune disease arising from the action of multiple genetic and environmental risk factors. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs1990760, of the interferon induced with helicase C domain 1 (IFIH1) gene with SLE in a Chinese population. A total of 877 SLE patients and 978 healthy control subjects were enrolled in the present study. The genotype of the IFIH1 rs1990760 polymorphism was determined by Sequenom MassARRAY technology. The IFIH1 rs1990760 T allele was significantly increased in patient group compared with control subjects (T versus C, Odds ratio?=?1.20, 95 % confidence interval?=?1.02–1.40). However, no significant difference in genotype distribution was found between cases and controls (P?=?0.07). No significant evidence was detected for the association of the IFIH1 rs1990760 polymorphism with SLE under neither dominant nor recessive model (TT + TC versus CC, P?=?0.06; TT versus TC + CC, P?=?0.08). We also analyzed the association of the IFIH1 rs1990760 T allele with clinical features, whereas no significant signal was found. In conclusion, our study represents the first report demonstrating an association of the IFIH1 rs1990760 polymorphism with SLE susceptibility in a Chinese population.     

Association of AIRE Polymorphisms with Genetic Susceptibility to Rheumatoid Arthritis in a Chinese Population

Recently, genetic polymorphisms within the autoimmune regulator (AIRE) have been implicated in the genetic susceptibility to rheumatoid arthritis (RA) in Japanese and Spanish. The aim of this case–control study involving 232 patients with RA and 313 ethnically matched control subjects was to investigate the association of AIRE rs2075876 and rs760426 polymorphisms with genetic predisposition to RA in a Chinese population. The genotypes of AIRE rs2075876 and rs760426 polymorphisms were determined by SNaPshot assay. A significant difference in the allele frequency of AIRE rs2075876 polymorphism between cases and controls was detected (A versus G, OR 1.33, 95 %CI 1.04–1.69, P?=?0.02, P corrected (Bonferroni correction) Pc?=?0.04). Significant evidence was found for the association between the minor allele A of AIRE rs2075876 polymorphism and the risk of RA under the recessive model (AA versus AG?+?GG, P?=?7.15?×?10^?3, Pc?=?1.43?×?10^?2). The frequency of the minor allele G of AIRE rs760426 polymorphism was higher in patients compared with controls (47.8 % versus 42.1 %), and this deviation showed a trend towards significant level (P?=?0.06, Pc?=?0.12). The association between the minor allele G of AIRE rs760426 polymorphism with RA risk under the dominant model and the recessive model revealed that significant evidence was detected under the recessive model (GG versus GA?+?AA, P?=?0.02, Pc?=?0.04). Our results indicated that AIRE rs2075876 and rs760426 polymorphisms were involved in the genetic background of RA in the Chinese population.     

A Single Nucleotide Polymorphism of IL-21 Gene is Associated with Systemic Lupus Erythematosus in a Chinese Population

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in IL-21 gene with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A total of 605 independent SLE patients and 666 unrelated healthy controls were recruited for the case?Ccontrol association study. Two SNPs (rs2221903 and rs907715) within the IL-21 gene intronic region were genotyped by TaqMan SNP allelic discrimination methods. The allele T frequency of SNP rs2221903 in patients and healthy controls was 89.4?% and 86.8?%, respectively [T versus C, odds ratio (OR)?=?1.287, 95?% confidence interval (CI)?=?1.010?C1.640]. No significant differences in genotype frequencies were shown between SLE patients and healthy controls (P value?=?0.705, 0.406, respectively). However, the effect of recessive model (TT versus CC?+?CT, OR?=?1.368, 95?% CI?=?1.050?C1.781) was observed. Distributions of allele and genotype frequencies of the SNP rs907715 showed no significant differences between SLE patients and controls. Analysis of the haplotypes revealed that CC haplotype was significantly associated with SLE (OR?=?0.734, 95?% CI?=?0.573?C0.941). In conclusion, our findings suggest that a SNP (rs2221903) and CC haplotype (rs2221903 and rs907715) of the IL-21 gene is associated with SLE in the Chinese population. However, further studies are needed to determine the functional consequences of this polymorphism with SLE susceptibility.     

Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus

Emerging evidences were accumulated to support the view that aberrant interleukin-7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P?=?0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P?=?0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P?=?0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene.     

Association study of interleukin-19 rs2243188 polymorphism with systemic lupus erythematosus in a Chinese population

Abstract

The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP), rs2243188 of interleukin-19 (IL-19), show significant evidence for association with SLE in a Chinese population. A total of 545 SLE patients and 613 healthy controls were collected in the present study. The genotyping of IL-19 rs2243188 polymorphism was detected by TaqMan allele discrimination assay on the 7300 real time polymorphism chain reaction system. The minor C allele of rs2243188, relative to the major A allele, appeared to have a significantly lower frequency in SLE patients (31.0%) as compared with controls (35.5%) (χ²?=?5.19, p?=?0.023). We also discovered a statistical significance in the dominant model (CC?+?CA versus AA: OR?=?0.755, 95% CI?=?0.598–0.953, p?=?0.018). However, no significant difference in genotype distribution was found between SLE patients and controls (p?=?0.056). Furthermore, an increased frequency of CC genotype were also detected in lupus nephritis (LN) groups as compared with non-LN groups (p?=?0.024). Besides, the individuals with CC genotype had a 2.201-fold higher risk for the susceptibility to LN than those A allele carriers (AA?+?CA) (p?=?0.006). Unfortunately, the analyses on the relationship of IL-19 rs2243188 with several clinical manifestations of SLE failed to find any significant results. In conclusion, our observations suggested the minor C allele of SNP rs2243188 might be a protective factor for SLE in a Chinese Han population. Moreover, the subgroup analysis highlighted that IL-19 rs2243188 SNP was associated with the susceptibility to LN patients.     

Interferon regulatory factor 3 as key element of the interferon signature in plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel genetic associations in the Mexican mestizo population

Many genetic studies have found an association between interferon regulatory factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE); however, specific dendritic cell (DC) alterations have not been assessed. The aim of the present study was to address the expression of IRF3 and IRF5 on different DC subsets from SLE patients, as well as their association with interferon (IFN)-α production and novel SNPs. For the genetic association analyses, 156 SLE patients and 272 healthy controls from the Mexican mestizo population were included. From these, 36 patients and 36 controls were included for functional analysis. Two IRF3 SNPs − rs2304206 and rs2304204 – were determined. We found an increased percentage of circulating pDC in SLE patients in comparison to controls (8·04 ± 1·48 versus 3·35 ± 0·8, P = 0·032). We also observed enhanced expression of IRF3 (64 ± 6·36 versus 36·1 ± 5·57, P = 0·004) and IRF5 (40 ± 5·25 versus 22·5 ± 2·6%, P = 0·010) restricted to this circulating pDC subset from SLE patients versus healthy controls. This finding was associated with higher IFN-α serum levels in SLE (160·2 ± 21 versus 106·1 ± 14 pg/ml, P = 0·036). Moreover, the IRF3 rs2304206 polymorphism was associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence interval (CI) = 2·401 (1·187–4·858), P = 0·021] as well as enhanced levels of serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings suggest that the predominant IRF3 expression on circulating pDC is a key element for the increased IFN-α activation based on the interplay between the rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican mestizo SLE patients.     

Meta-analysis of TNF-α promoter − 238A/G polymorphism and SLE susceptibility

The tumor necrosis factor-α (TNF-α) promoter ? 238A/G polymorphism has been repeatedly associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. Our aim was to do a meta-analysis to assess the association between TNF-α promoter ? 238A/G polymorphism and SLE. Eleven published studies of this polymorphism with SLE in different ethnic groups were identified using a Medline search. Meta-analysis was performed for genotypes AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele in a fixed/random effect model. The overall odds ratio (OR) of the AA versus GG+GA genotypes was 3.46 (95% CI = 1.35–8.83, P = 0.01), and a similar result was found in Caucasian population (OR = 4.62, 95% CI = 1.20–17.80, P = 0.03); the overall OR of the AA versus GG genotypes was 3.36 (95% CI = 1.32–8.55, P = 0.01), and a similar result was found in Caucasian population (OR = 4.29, 95% CI = 1.11–16.53, P = 0.03); the OR of the GA versus GG genotypes was 0.48 (95% CI = 0.30–0.75, P = 0.001) in Caucasian population. In conclusion, this meta-analysis demonstrates the association between TNF-α promoter ? 238A/G polymorphism and SLE, especially in Caucasian population.     

Association of STAT4 rs7574865 with Susceptibility to Systemic Lupus Erythematosus in Iranian Population

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex genetic inheritance that affecting different organs and systems. STAT4 has been newly identified as a susceptible gene in the development of SLE. According to recent studies, STAT4 has been associated with SLE in various populations. We investigated whether STAT4 single nucleotide polymorphisms (SNPs) were associated with susceptibility and clinical features of SLE in Iranian patients. The study group comprised 280 patients with SLE and 281 sex-, age-, and ethnicity-matched healthy controls of Iranian ancestry. Two SNPs (rs7574865 and rs7601754) were genotyped using the TaqMan MGB Allelic Discrimination method. Our results showed a significant association betweenrs7574865 T allele (odds ratio (OR)?=?1.50, 95 % CI?=?1.18–1.92, P?=?0.002) and susceptibility to SLE. The rs7574865TT genotype (P?=?0.02, OR?=?1.94, 95 % CI?=?1.74–3.19) and GT genotype (P?=?0.008, OR?=?1.71, 95 % CI?=?1.19–2.45) showed a significant association with the risk of SLE in the Iranian population. We concluded that STAT4 rs7574865 is associated with SLE susceptibility in the Iranian population and this SNP might be a factor in the pathogenesis of SLE. However, further studies are required to investigate the mechanism by which polymorphisms in this gene lead to SLE.     

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

Objective

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).

Materials and methods

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.

Results

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.

Conclusions

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.     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

Functional variants of TNFAIP3 are associated with systemic lupus erythematosus in a cohort of Chinese Han population

Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) is a negative regulator of NF-κB activity. We previously reported that the paired tandem polymorphic dinucleotides TT > A (rs148314165, rs200820567 of TNFAIP3) conferred the risk for systemic lupus erythematosus (SLE) in European and Korean populations. We investigated the genetic association of the TT > A variants, as well as the functional coding variant rs2230926 in exon 3 of TNFAIP3 in 1229 Chinese Han SLE patients and 1608 matched population controls. We further evaluated the role of these variants in regulating expression of the TNFAIP3 gene and NF-κB signaling pathway in their peripheral blood mononuclear cells from Chinese SLE patients. The TT > A variants and the TNFAIP3 exon 3 coding variant rs2230926 demonstrated significant associations in SLE (P_{TT > A} = 8.96 × 10^?12, odds ratio [OR] = 2.07, 95% confidence interval [CI] = 1.68–2.55). SLE patients carrying the risk A allele showed reduced messenger RNA expression of the TNFAIP3 gene and increased expression of NF-κB1 in PBMCs. Conditional analyses revealed that the TT > A variants are likely to be causal variants in Chinese Han SLE patients. The TT > A variants associated with Chinese Han SLE and negatively regulate the expression of the TNFAIP3 gene resulting in enhanced NF-κB activity.     

Association between the interaction of SMAD3 polymorphisms with body mass index and osteoarthritis susceptibility

Purpose: This study aimed to investigate the relationship between the interaction of SMAD3 polymorphisms (rs12102171 and rs2289263) with body mass index (BMI) and osteoarthritis (OA) susceptibility. Methods: This study involved 112 OA patients and 120 healthy people. The controls were frequency-matched with the cases by age and sex. Hardy-Weinberg equilibrium (HWE) was tested by χ² test in the control group. The rs12102171 and rs2289263 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relative risk of OA was represented by odds ratio (OR) with 95% confidence interval (CI) calculated by chi-squared test. Gene-environment interaction was analyzed by crossover analysis. Results: The TT genotype and T allele of SMAD3 rs12102171 polymorphism were more frequent in case than control groups (P=0.04 in both of two polymorphisms), which increased the risk of OA (OR=3.39, 95% CI=1.03-11.11 and OR=1.64, 95% CI=1.03-2.59). GG genotype and G allele were also the risk factors for OA (OR=3.22, 95% CI=1.09-9.51 and OR=1.57, 95% CI=1.02-2.42). The BMI had interactions with genotype CC and CT+TT of rs12102171 and TT and TG+GG of rs2289263 (rs12102171: OR=2.15, P=0.02 and OR=3.99, P=1.00×10^-3; rs2289263: OR=2.73, P=4.00×10^-3 and OR=4.67, P=0). Conclusions: CC and CT+TT and TT and TG+GG genotypes of SMAD3 rs12102171 and rs2289263 polymorphisms together with BMI may be susceptible factors to OA, and interactions there between can possibly confer risk to OA.     

Estrogen receptor alpha gene (ESR1) polymorphism and its interaction with smoking and drinking contribute to susceptibility of systemic lupus erythematosus

The aim of this study is to investigate the association of estrogen receptor alpha gene (ESR1) polymorphisms, additional gene–gene, and gene–environment interaction with systemic lupus erythematosus (SLE) risk. SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats) was used to investigate the Hardy–Weinberg equilibrium (HWE) in controls and association between SNP and SLE risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the interactions among SNPs and environmental risk factors; SLE risk was significantly higher in carriers of rs2234693 C allele than those with TT (TC + CC versus TT), adjusted OR (95%CI) = 1.57 (1.21–2.06), and was also higher in carriers of rs9340799 G allele than those with AA (AG + GG versus AA), adjusted OR (95%CI) = 1.68 (1.24–2.13). However, we also find no association between rs2228480 and SLE risk after covariates adjustment. We found a significant two-locus model (p = 0.0010) involving rs2234693 and smoking; the cross-validation consistency of this model was 10/10, and the testing accuracy was 62.70%. Smokers with TC or CC of rs2234693 genotype have the highest SLE risk, compared to never-smokers with TT of rs2234693 genotype, OR (95%CI) was 2.50 (1.65–3.42), after covariates adjustment for gender, age, alcohol drinking, and BMI. We found that C allele of rs2234693 and G allele of rs9340799 within ESR1 gene, their interaction between rs2234693 and current smoking were all associated with increased SLE risk.     

Association between IL-33 Gene Polymorphisms (rs1929992, rs7044343) and Systemic Lupus Erythematosus in a Chinese Han Population

Objective: Interleukin-33 (IL-33) is a member of the IL-1 family, and previous studies found the single-nucleotide polymorphisms (SNPs) in the IL-33 gene was related to susceptibility to autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis and Behcet’s disease. To date, no study has discussed the potential association between IL-33 gene polymorphisms and systemic lupus erythematosus (SLE).

Methods: We conducted a case-control study including 371 SLE patients and 408 healthy controls to investigate the correlation between the SNPs of IL-33 gene (rs1929992, rs7044343) and SLE in a Chinese Han population.

Results: There was significantly lower expression of allele G for rs1929992 in SLE patients than that in controls (G versus A, P = 0.012, OR = 1.310, 95% CI: 1.060–1.624 after adjustment with sex). Similarly, genotype GG was associated with the susceptibility to SLE as compared with the AA genotype (P = 0.017, OR = 1.714, 95% CI: 1.101–2.669 after adjustment with sex). We also found statistical significance in the dominant model (GG+GA versus AA, P = 0.017, OR = 1.481, 95% CI: 1.074–2.044 after adjustment with sex). However, we found no strong evidence for the association of IL-33 rs7044343 polymorphism with SLE. Moreover, association studies were performed on the relationship between the IL-33 gene polymorphisms and lupus nephritis as well as nine clinical features of SLE, but there was no significant association regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of sub-phenotypes.

Conclusion: Our findings indicate that IL-33 rs1929992 polymorphism may be a potential biomarker for susceptibility to SLE.     

Association of CAV1 polymorphisms with the risks of breast cancer: A systematic review and meta-analysis

BackgroundCaveolin-1 (CAV1) polymorphisms have been shown to correlated with breast cancer risk in previous studies. However, the role of CAV1 polymorphisms still remained indecisive, and dual functions of CAV1 was demonstrated in breast cancer development. Consequently, a meta-analysis to evaluate and summarize the association of the CAV1 polymorphisms with breast cancer susceptibility.Material and methodsExtensive search was performed in PubMed, Web of Science, Google scholar, EMBASE.com, CNKI and Wanfang searching platform up to March 2019. The Newcastle–Ottawa Scale (NOS) were used to evaluate the quality of each study. The Odds ratios (ORs) and the 95% confidence intervals (CIs) were analyzed to evaluate the strength of the associations in five genetic models. Inter-study heterogeneity was quantified using the I-squared (I²) test. In addition, the Egger’s test and Begg’s test were applied to evaluate the publication bias.Results4 case-control studies with 2115 cases and 2138 controls were enrolled into this analysis. There was a significant association between rs3807987 polymorphism of CAV1 and breast cancer in allele comparison (A vs. G: OR = 1.288, 95％CI = 1.162–1.428, P < 0.001), heterozygote comparison (AG vs. GG: OR= 1.422, 95％CI=1.233–1.639, P < 0.001), and dominant comparison (AA+AG vs. GG: OR=1.395, 95％CI=1.228-1.586, P < 0.001). A significant association of rs3807987 polymorphism in allele comparison (A vs. G: OR=1.238, 95％CI=1.109–1.383, P < 0.001), heterozygote comparison (AG VS. GG: OR=1.466, 95％CI=1.267–1.697, P < 0.05), and dominant comparison (AA+AG vs. GG: OR=1.384, 95％CI=1.209–1.585, P < 0.001) was also founded amongst Chinese population. A significant association between rs7804372 polymorphism and breast cancer amongst Chinese population in recessive comparison (AA vs. AT + TT: OR = 0.730, 95％CI = 0.567–0.940, P = 0.015) was identified. No significant association between breast cancer risk and rs1997623 was found.ConclusionCAV1 rs3807987 and rs7804372 polymorphisms are associated with the change of breast cancer risk. More well-designed and large studies in various populations are needed to further elaborate these associations.     

TNF-α-308 promoter G/A and PTPN22 (1858 C/T) genes polymorphisms in Egyptian patients with systemic lupus erythematosus

Tumor necrosis factor alpha (TNF-α) promoter gene polymorphism at position 308 and that of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) at position 1858 C/T have been inconsistently implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. We investigated the possible association of these polymorphisms with SLE susceptibility, and whether serum TNF-α level is related to different genotypes and disease activity in Egyptian SLE patients. TNF-α-308 G/A and PTPN22 C1858T polymorphisms were determined by PCR-restriction fragment length polymorphism analysis in 40 SLE patients and 40 unrelated healthy controls. Serum TNF-α level was measured by ELISA method. The median serum TNF-α was significantly higher in SLE patients than in controls (P?<?0.001). A significant positive correlation was detected between serum TNF-α and SLE activity index (r?=?0.723, P?<?0.001). There was no significant difference in TNF-α-308 G/A genotypes or allele frequency between SLE cases and controls (P?=?0.108 and P?=?0.133, respectively). Diabetes was the only clinical feature in SLE patients that showed significant higher frequency with GA genotype than with GG genotype (P?=?0.001). Risk estimation for the TNF-α-308 genotypes was of no significant (odds ratio?=?2.429; 95 % CI?=?0.8–7.2; P?=?0.108). Concerning PTPN22 1858 C/T, there was no significant difference in PTPN22 C/T genotypes or allele frequency between SLE cases and controls (P?=?0.152 and P?=?0.155, respectively). TNF-α-308 G/A and PTPN22 (1858 C/T) polymorphisms do not exhibit a significant influence on the susceptibility of SLE in Egyptian patients. However, serum TNF-α level could be a sensitive marker of SLE disease activity.     

Serum Leptin Levels,Leptin Receptor Gene (LEPR) Polymorphism,and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln?>?Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG?+?GG) in cases compared to controls [OR?=?2.52, CI?=?1.18–5.35, p?=?0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR?=?1.49, p?=?0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR?=?11.8, CI?=?1.6–85.1, p?=?0.002] and an inverse association with cardiac disorder [OR?=?0.09, CI?=?0.02–0.46, p?=?0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9?±?19.5 vs 14.8?±?10.4, p?<?0.001). SLE patients in the highest quartile leptin levels (≥32.5?ng/mL) were significantly more likely to have higher BMI (p?=?0.001) and increased risk of developing arthritis (p?=?0.02). Furthermore positive association was observed between the variant genotype(AG?+?GG) and leptin levels (p?=?0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.     

Genetic association between CD44 polymorphisms and chronic hepatitis B virus infection in a Chinese Han population

Aims: This article aimed at discussing the association of chronic hepatitis B virus (HBV) infection with CD44 polymorphisms in Chinese Han population; meanwhile, the interaction of polymorphisms was also analyzed based on chronic HBV infection. Methods: The genotyping of CD44 polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 108 HBV infected and 130 healthy persons. The genotype distributions of CD44 rs187115, rs13347 in the control group were checked by Hardy-Weinberg equilibrium (HWE). The strength of the relevance between polymorphism and disease was measured by odds ratio (OR) with corresponding 95% confidence interval (CI) calculated by χ² test. The 2×4 crossover analysis method was used to conduct the interaction analysis of polymorphisms. Results: The genotype distributions in controls conformed to HWE. GG genotype and G allele frequencies in rs187115 were obviously higher in cases than the controls (P=0.02, 0.04). Compared with the common genotype CC, individual who carried mutant genotypes (CT and TT) of rs13347 had a significantly high risk to suffer from HBV infection (OR=1.99, P=0.02 for CT; OR=3.56, P=3.00×10^-3 for TT), furthermore, CT+TT genotype also showed a high susceptibility (OR=2.27, P=2.00×10^-3). Similarly, T allele of rs13347 increased 0.98 times risk in cases compared with controls (OR=1.98, 95% CI=1.34-2.92). The two polymorphisms in CD44 presented a positive interaction. Conclusion: CD44 polymorphisms are associated with chronic HBV infection as the risk factors, and the synergistic action is also found between the two polymorphisms.     

Fc受体γ链基因启动子区-29位点基因多态性与系统性红斑狼疮关系的研究

目的:探讨Fc受体γ链基因启动子区-29位点基因多态现象在中国南方人群中的分布及其与系统性红斑狼疮(SLE)易感性和临床表现的关系。方法:采用PCR-RFLP方法检测180例SLE患者和140例正常对照组Fc受体γ链基因启动子区-29位点基因型。结果:SLE患者Fc受体γ链基因启动子区-29位点TT基因型频率(33.3%)及T等位基因频率(54.4%)明显高于正常对照组(17.2%及42.9%)(P＜0.05), 而GG基因型频率(24.4%)及G等位基因频率(45.6%)明显低于正常对照组(31.4%及57.1%)(P＜0.05)。T等位基因的比值比为1.59。SLE患者各基因型频率及各等位基因频率与狼疮性肾炎(LN)无相关关系(P＞0.05)。结论:SLE患者Fc受体γ链基因启动子区-29位点T等位基因与SLE发病相关但与LN的发生无关。