Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

OBJECTIVE: Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin α(M) (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. METHODS: The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. RESULTS: The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (OR(meta)=1.16, 95% CI 1.11 to 1.22; p=4.88×10(-10) and OR(meta)=1.67, 95% CI 1.55 to 1.79; p=3.32×10(-46), respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10(-5)). CONCLUSION: These findings are the first to suggest that an ICAM-integrin-mediated pathway contributes to susceptibility to SLE.     

Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms

OBJECTIVE: To determine whether the IRF5 gene, which encodes interferon regulatory factor 5, is associated with systemic lupus erythematosus (SLE) in a Japanese population. METHODS: A case-control study was performed in 277 SLE patients and 201 healthy controls. Associations between the IRF5 genotype and levels of messenger RNA (mRNA) for interferon (IFN) pathway genes were examined using an mRNA expression database of HapMap samples. RESULTS: Carriers of the rs2004640T single-nucleotide polymorphism (SNP) were slightly increased among SLE patients (58.8%) as compared with controls (50.2%). When data from our Japanese population were combined with previously published data from a Korean population, the T allele frequency was found to be significantly increased in SLE patients (P = 8.3 x 10(-5)). While no association was observed for the rs10954213 SNP or the exon 6 insertion/deletion, significant associations with 3 intron 1 SNPs (-4001, rs6953165, and rs41298401) were found. The allele frequency of rs41298401G was significantly decreased in SLE patients (13.0% versus 18.7% in controls; P = 0.017), and the allele frequency of rs6953165G, which was in absolute linkage disequilibrium with -4001A, was increased in SLE patients (8.8% versus 5.2% in controls; P = 0.034). The Caucasian risk haplotype was not present; instead, a protective haplotype carrying rs2004640G, rs41298401G, the deletion in exon 6, and rs10954213A was identified. SNP rs10954213, but not intron 1 SNPs, was associated with IRF5 at the mRNA level; nevertheless, intron 1 SNPs were also associated with levels of mRNA for several IFN pathway genes, suggesting a functional role. CONCLUSION: IRF5 was found to be associated with SLE in Asian populations. Intron 1 SNPs, rather than exon 6 and 3'-untranslated region polymorphisms, appeared to play a crucial role.     

miRNA-17-5p在慢加急性肝衰竭合并乙型病毒性肝炎患者中的表达及与自噬相关蛋白表达的关系

目的:探讨微小RNA-17-5p(miRNA-17-5p)在慢加急性肝衰竭合并乙型肝炎(HBV-ACLF)患者中的表达水平及其与自噬相关蛋白Beclin1、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)表达的相关性。方法:选取2019年2月至2020年5月HBV-ACLF住院患者82例为HBV-ACLF组,选取同期住院治疗的慢性乙型肝炎(CHB)患者79例作为CHB组,选取同期健康体检者86例作为对照组。采用实时荧光定量PCR(qRT-PCR)法检测血清miRNA-17-5p水平;酶联免疫吸附(ELISA)法检测血清Beclin1、LC3-Ⅱ、总胆红素、白蛋白水平;PCR结合荧光探针的体外扩增技术测定血清HBV DNA载量;Pearson法分析HBV-ACLF患者血清miRNA-17-5p与Beclin1、LC3-Ⅱ、总胆红素、白蛋白、HBV DNA载量的相关性;受试者工作特征曲线(ROC)分析血清miRNA-17-5p、Beclin1、LC3-Ⅱ水平对HBV-ACLF的诊断价值;多因素Logistic回归分析影响HBV-ACLF发生的因素。结果:HBV-ACLF组患者血清Beclin1、LC3-Ⅱ、总胆红素水平高于CHB组和对照组,miRNA-17-5p、白蛋白低于CHB组和对照组(P<0.05);CHB组患者血清Beclin1、LC3-Ⅱ、总胆红素水平高于对照组,miRNA-17-5p、白蛋白低于对照组(P<0.05);HBV-ACLF组患者血清HBV DNA载量高于CHB组(P<0.05)。HBV-ACLF组患者血清miRNA-17-5p水平与Beclin1、LC3-Ⅱ呈负相关(r=-0.580、-0.511;均P<0.05);Beclin1、LC3-Ⅱ与总胆红素、HBV DNA载量均呈正相关,与白蛋白呈负相关(P<0.05);miRNA-17-5p与总胆红素、HBV DNA载量均呈负相关,与白蛋白呈正相关(P<0.05)。血清miRNA-17-5p、Beclin1、LC3-Ⅱ水平诊断HBV-ACLF的曲线下面积(AUC)分别为0.862、0.784、0.886,特异性分别为88.4%、80.2%、81.4%,敏感度分别为74.4%、63.4%、81.7%;三者联合诊断的AUC为0.915,特异性为88.4%,敏感度为82.9%。Beclin1、HBV DNA载量是影响HBV-ACLF发生的独立危险因素(P<0.05),miRNA-17-5p是影响HBV-ACLF发生的保护因素(P<0.05)。结论:HBV ACLF患者血清miRNA-17-5p表达水平降低,与Beclin1、LC3-Ⅱ呈明显负相关,且三者均对HBV-ACLF有一定的诊断价值。     

血管紧张素转化酶基因多态性与系统性红斑狼疮相关性研究

目的探讨位于人类17号染色体长臂2区3带(17q23)上的血管紧张素转化酶(ACE)基因多态性G261T与系统性红斑狼疮(SLE)的关系。方法采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)方法检测人类17q23上的ACE基因多态性G261T,运用家系为基础的相关性检验(FBAT)方法,对119个中国汉族SLE患者家系(其中核心家系95个,119例患者,316名家系其他成员)ACE多态性位点(rs4303)进行等位基因和基因型分析。结果在119例SLE患者中：G、T等位基凶频率分别是44．8%和55．2%：基因型GG、GT和TT的频率分别是13．9%,62．0%,24．1%。FBAT单位点分析显示G261T多态性与SLE显著相关：附加模型(Z=2．877．P=0．004),显性模型(Z=2．557,P=0．011)以及隐性模型(Z= 2．202,P=0．028)。传递不平衡检验(TDT)和同胞传递不平衡检验(STDT)显示其中ACE-261T等位基因由杂合子父母优势传递给患病子女或者与正常同胞相比更容易传递给患者(X~2=11．66,P=0．001)。结论ACE基因是中国汉族人群SLE的易感基因；其中ACE-261T等位基因与SLE发病相关。     

A functional role for NS5ATP9 in the induction of HCV NS5A‐mediated autophagy

Autophagy has been shown to facilitate replication of hepatitis C virus (HCV); however, the mechanism by which HCV induces autophagy has not been fully established. NS5A, a nonstructural protein expressed by HCV, regulates numerous cellular pathways, including autophagy, by up‐regulating Beclin 1; however, the underlying mechanism remains unclear. To obtain new insights into HCV‐regulated autophagy, NS5ATP9 was overexpressed in HepG2 and L02 cells, resulting in up‐regulation of endogenous Beclin 1 mRNA and protein levels, respectively. The luciferase‐reporter assay results showed that both NS5A and NS5ATP9 could transactivate Beclin 1 promoter activity, but that NS5A could not transactivate the Beclin 1 promoter in NS5ATP9‐silenced HepG2 and L02 cells. Up‐regulation of Beclin 1 mRNA and protein expression by NS5A could also be attenuated by NS5ATP9 knock‐down. Furthermore, the HepG2 and L02 cells that transiently overexpressed NS5ATP9 had enhanced accumulation of vacuoles carrying the autophagy marker LC3, consistent with the conversion of endogenous LC3‐I to LC3‐II. In contrast, the conversion of endogenous LC3‐I to LC3‐II could not be enhanced by NS5A in NS5ATP9‐silenced HepG2 cells. These results highlight an important potential role for NS5ATP9 in HCV NS5A‐induced hepatocyte autophagy.     

NOD2/CARD15 , ATG16L1 and IL23R gene polymorphisms and childhood-onset of Crohn’s disease

AIM: To assess whether the polymorphisms of NOD2/ CARD15 , autophagy-related 16-like 1 (ATG16L1 ), and interleukin-23 receptor (IL23R ) genes play a more critical role in the susceptibility of childhood-onset than in adult-onset Crohn’s disease (CD). METHODS: Polymorphisms R702W, G908R, and 3020insC of NOD2/CARD15 ; rs2241880 A/G of ATG16L1 , and rs11209026 (R381Q) of IL23R gene were assessed in 110 childhood-onset CD, 364 adult-onset CD, and 539 healthy individuals. Analysis of polymorphisms R702W, G908R, ...     

Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects

OBJECTIVE: The A allele of the PD1.3 single-nucleotide polymorphism (SNP) on the programmed cell death gene PDCD1 was markedly more frequent in patients with systemic lupus erythematosus (SLE) than in unaffected controls in a recent study involving large sets of Swedish, European American, and Mexican families. This study sought to determine the role of PDCD1 in susceptibility to SLE in the Spanish population. METHODS: Seven PDCD1 SNPs were studied in 518 SLE patients and 800 healthy control subjects who had been recruited in 5 distant towns spanning continental Spain. Patients and controls were of Spanish ancestry. The diagnosis of SLE was in accordance with the American College of Rheumatology updated classification criteria. RESULTS: The A allele of the PD1.3 polymorphism was significantly less frequent in Spanish female patients with SLE than in Spanish female controls (9.0% versus 13.0%, odds ratio 0.67, 95% confidence interval 0.50-0.89). This difference was consistent across the 5 sets of samples grouped by town of recruitment. The other PDCD1 SNPs were not associated with SLE susceptibility. The haplotype structure of PDCD1 in the Spanish controls was different from that reported in other healthy control populations. CONCLUSION: Our results confirm the association of PDCD1 with susceptibility to SLE, but the findings show a lack of involvement of the PD1.3 SNP, which is contrary to the role of the PD1.3 A allele observed previously. These contradictory results probably reflect population differences in the haplotype structure of the PDCD1 locus. More research focusing on new polymorphisms and identifying associations in other populations will be needed to clarify the role of PDCD1 in SLE susceptibility.     

A variant in microRNA-196a2 is not associated with susceptibility to and progression of colorectal cancer in Chinese

Background: MicroRNAs (miRNAs) are small non‐coding RNAs with regulatory functions as tumour suppressors and oncogenes. Although single nucleotide polymorphism (SNP) in miRNA regions have been reported to be rare and unlikely to be functionally important, recent evidence suggested that rs11614913 SNP in miR‐196a2 was associated with the susceptibility of lung cancer, breast cancer, congenital heart disease and shortened survival time of non‐small‐cell lung cancer. Aims: The aim of this study was to investigate the association between this genetic variant and the risk and/or progression of colorectal cancer (CRC). Methods: A total of 126 CRC patients and 407 healthy controls was periodically enrolled. DNA was extracted from blood specimens, and miR‐196a2 polymorphism was genotyped by polymerase chain reaction–ligation detection reaction (PCR–LDR). Results: Although the frequency of CC homozygotes or miR‐196a2C allele‐containing genotypes (CT and CC) was lower in CRC patients than in the healthy controls, no significant association between miR‐196a2 polymorphism and the risk of CRC was found. The frequency of the ‘C’ allele in CRC patients was also not significantly lower than in healthy controls. In a subsequent analysis of the association between this polymorphism and the progression of CRC, there was still no significant difference in both genotype and allelic frequency. Conclusions: Our results suggest that miR‐196a2 polymorphism is not associated with both an increased risk and progression of CRC in Chinese.     

活动性系统性红斑狼疮自噬及相关基因研究

目的 观察活动性系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)的自噬现象并检测相关基因的表达水平. 方法 以初诊及新发作的活动性SLE患者20例为病例组,类风湿关节炎(RA)患者10例和健康志愿者10名分别作为对照组.密度梯度离心法分离PBMC,并利用贴壁法除去单核细胞.运用透射电镜(TEM)观察细胞的超微结构,半定量反转录-聚合酶链反应(RT-PCR)及实时定量RT-PCR检测各组PBMC中Beclin1、微管相关蛋白1轻链3(MAPLC3)mRNA的表达水平. 结果 TEM发现活动性SLE患者PBMC中存在自噬现象;Beclinl和MAPLC3 mRNA在活动性SLE患者表达量均增高,且分别较RA组和健康对照组表达差异有统计学意义. 结论 活动性SLE患者外周血PBMC存在自噬现象,且细胞自噬相关基因表达较健康对照组和RA组增强,这可能与SLE的发生、发展相关.     

A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus

STAT4 has been newly identified as a susceptibility gene for systemic lupus erythematosus (SLE) in recent reports. To more precisely estimate the association between STAT4 polymorphism and SLE risk, a meta-analysis was performed. Studies on the association of STAT4 rs7574865 or rs7601754 with SLE were fully considered and carefully selected using three electronic databases (PubMed, Embase, and Web of Science). A total of 17 comparisons from 8 relevant studies involving 7,381 patients and 11,431 controls were included to analyze the association between STAT4 rs7574865 and SLE risk. The pooled OR for the minor T allele of STAT4 rs7574865 was 1.65 (95% CI 1.56–1.75, P < 0.001) in SLE. In a subgroup analysis by ethnicity, the degree of risk of STAT4 rs7574865 with SLE susceptibility was similar in populations of European or Asian origin, although significant differences in the minor T allele frequencies were observed in the two population controls. As for rs7601754, there were five comparisons from four relevant studies involving 2,498 patients and 4,825 controls in this meta-analysis. The pooled OR for the minor C allele of STAT4 rs7601754 was 0.67 (95% CI 0.59–0.75, P < 0.001) in SLE. Conversely, the major T allele of STAT4 rs7601754 might be a risk factor for SLE risk. In conclusion, our results do support STAT4 rs7574865 polymorphism as a susceptibility factor for SLE in populations of European and Asian origin. Our results also suggest that STAT4 rs7601754 polymorphism might be associated with SLE risk.     

The Impact of Interleukin 28b Gene Polymorphism on the Virological Response to Combined Pegylated Interferon and Ribavirin Therapy in Chronic HCV Genotype 4 Infected Egyptian Patients Using Data Mining Analysis

Background: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1.Objectives: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis.Patients and Methods: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene.Results: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response.Conclusions: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.     

The functional p53 codon 72 polymorphism is associated with systemic lupus erythematosus

The aim of the study is to investigate whether the functional p53 codon 72 polymorphism is associated with susceptibility to SLE and its clinical features. A polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the p53 codon 72 in 90 SLE patients and 114 healthy controls. Clinical/serological manifestations were analysed in each patient and correlated with the genotypes. The OR of the association of the Pro allele with SLE was 1.70 (95% CI, 1.15-2.53, P = 0.0079) and the OR of the Pro/Pro (a recessive model) was significantly increased (OR = 2.58, 95% CI = 1.24-5.39, P = 0.0093). The Armitage's trend test indicated a significant dosage effect of the Pro allele for SLE (OR = 1.73, chi-square = 7.08, P = 0.0078). However, there was no significant association of the polymorphism with clinical/serological manifestations studied here. In conclusion, our finding suggests the functional p53 codon 72 polymorphism may be associated with SLE susceptibility, suggesting individuals who carry the Pro allele may have a higher risk to SLE susceptibility than those with the Arg allele. Further studies for replications are needed to confirm that the p53 polymorphism contributes to SLE.     

ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with celiac disease in the Netherlands

BACKGROUND: Inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--and celiac disease are intestinal inflammatory disorders with a complex genetic background. Recently, two novel genes were found to be associated with IBD susceptibility. One, an uncommon coding variant (rs11209026) in the gene encoding for the interleukin-23 receptor (IL23R), conferred strong protection against CD. The other, rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1), was associated with CD. We performed a case-control study for the association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at the association of IL23R and ATG16L1 with celiac disease. METHODS: Five hundred eighteen Dutch white IBD patients (311 CD and 207 UC, including 176 trios of patients with both parents), 508 celiac disease patients, and 893 healthy controls were studied for association with the rs11209026 (IL23R) and rs2241880 (ATG16L1) single nucleotide polymorphisms (SNP). RESULTS: The rs11209026 SNP in IL23R had a protective effect for IBD in the case-control analysis (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14, CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were associated with IL23R. For ATG16L1, the rs2241880 SNP was associated with CD susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in CD. No association was found between IL23R or ATG16L1 and celiac disease. CONCLUSIONS: We confirmed the association of IL23R and ATG16L1 with CD susceptibility and also the association of IL23R with UC. We found IL23R and ATG16L1 were not associated with celiac disease susceptibility.     

T300A polymorphism of ATG16L1 and susceptibility to inflammatory bowel diseases:A meta-analysis

AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn‘s disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when...     

Association between the rs2004640 functional polymorphism of interferon regulatory factor 5 and systemic lupus erythematosus: a meta-analysis

The aim of this study is to determine whether the functional interferon regulatory factor 5 (IRF5) polymorphism, rs2004640, confers susceptibility to systemic lupus erythematosus (SLE) in multiple ethic populations. A meta-analysis was conducted on the T allele of the IRF5 rs2004640 polymorphism and 12 studies were included in the meta-analysis. Meta-analysis revealed an association between SLE and the IRF5 rs2004640 T allele in all subjects without inter-study heterogeneity (OR 1.429, 95% CI 1.359–1.503, P < 0.001). The IRF5 rs2004640 T allele was significantly associated with SLE in European and Asians. The Asian population had a much lower prevalence of the T allele (34.4%) than any other population studied. and Europeans had the highest frequency of the IRF5 rs2004640 T allele (51.8%). In conclusion, 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.     

Associations of protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene polymorphisms with susceptibility to Graves' disease in a Japanese population

BACKGROUND: The polymorphism of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene, which encodes an important negative regulator of T cell activation, has been reported to be associated with susceptibility to Graves' disease (GD) in Caucasians. The objective of this study was to investigate whether PTPN22 gene polymorphisms confer susceptibility to GD and Graves' ophthalmopathy (GO) in a Japanese population. METHODS: We performed a case-control study of PTPN22 gene polymorphisms in Japanese GD patients (n = 414) and healthy control subjects with no antithyroid autoantibodies or family history of autoimmune disorders (n = 231). The G-1123C polymorphism (rs2488457) in the promoter region, Arg620Trp (C1858T) polymorphism (rs2476601) in exon 14, IMS-JST146695 polymorphism (rs3789607) in intron 19, and SNP37 (rs3789604) downstream of the PTPN22 gene were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism using restriction enzymes and direct PCR sequencing methods. RESULTS: None of the GD patients or control subjects had the 1858T allele of the PTPN22 gene polymorphism. The AA-genotype and A-allele frequencies of SNP37 were significantly higher in GD patients than in control subjects (A-allele frequency: p = 0.0085, odds ratio = 1.45). The genotype frequencies and allele frequencies of the G-1123C and IMS-JST146695 polymorphisms did not differ between GD patients and control subjects. The -1123G/1858C/JST146695T/SNP37C haplotype frequency was significantly lower in GD patients than in control subjects. There were no associations between PTPN22 gene polymorphisms and GO. CONCLUSIONS: The results suggest that SNP37 of the PTPN22 gene is associated with susceptibility to GD in a Japanese population. Further studies including functional analyses are required.     

Gene–gene interaction between CD40 and CD226 gene on systemic lupus erythematosus in the Chinese Han population

The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene–gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case–control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs. Logistic regression analysis showed that SLE risk was significantly higher in carriers of T allele of rs4810485 in CD40 gene than those with GG genotype (GT+ TT vs GG), adjusted OR (95 % CI) 1.84 (1.40–2.29). In addition, we also found SLE risk was also significantly higher in carriers of rs763361 T allele within CD226 gene than those with CC genotype (CT+ TT vs CC), adjusted OR (95 % CI) 1.89 (1.38–2.13). GMDR analysis suggested a potential gene–gene interaction between rs4810485 and rs763361. Overall, cross-validation consistency of the two-locus model was 10/10, and the testing accuracy was 62.17 %. We also found that subjects with GT or TT of rs4810485 and CT or TT of rs763361 genotype have the highest SLE risk, compared with subjects with GG of rs4810485 and CC of rs763361 genotype, and OR (95 % CI) was 2.14 (1.67–3.08), after covariates adjustment. Our results support an important association of rs4810485 in CD40 gene and rs763361 in CD226 gene polymorphism, combined effect of rs4810485 and rs763361 with increased risk of SLE.