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Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance.

ABSTRACT: Although rare variant C1Q deficiency was identified as causative risk for systemic lupus erythematosus (SLE), there are limited and inconsistent reports regarding the common polymorphisms of C1Q genes in SLE susceptibility. Furthermore, there are no reports concerning polymorphisms of C1S, C1R, and C1RL and whether they confer susceptibility to SLE. We therefore evaluated 22 SNPs across six C1-complex genes in two independent case-control cohorts, and identified four novel SNPs that confer protection from SLE. The four SNPs are all located in C1Q. Particularly, the variant rs653286 displayed an independent reduced risk on SLE susceptibility (OR 0.75, P?=?2.16?×?10-3) and anti-dsDNA antibodies (OR 0.68, P?=?0.024). By bioinformatics analysis, SNPs rs653286 and rs291985 displayed striking cis-eQTL effects on C1Q genes expression. Individuals homozygous for the 'protective' allele at four SNPs had significantly higher levels of serum C1q (rs680123-rs682658: P?=?0.0022; rs653286-rs291985: P?=?0.0076). To our knowledge, this is the first study to demonstrate that only C1Q polymorphisms are associated with SLE. The C1Q SNP rs653286 confers an independent protective effect on SLE susceptibility and affects transcript abundance.

SUBMITTER: Guo J

PROVIDER: S-EPMC5966390 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance.

Guo Jianping J Gao Yanyan Y Wang Yuxuan Y Zou Yundong Y Du Yan Y Luo Cainan C Shi Yamei Y Yang Yue Y Wu Xinyu X Su Yin Y Wu Lijun L Chen Shi S Li Zhanguo Z

Scientific reports 20180523 1

Although rare variant C1Q deficiency was identified as causative risk for systemic lupus erythematosus (SLE), there are limited and inconsistent reports regarding the common polymorphisms of C1Q genes in SLE susceptibility. Furthermore, there are no reports concerning polymorphisms of C1S, C1R, and C1RL and whether they confer susceptibility to SLE. We therefore evaluated 22 SNPs across six C1-complex genes in two independent case-control cohorts, and identified four novel SNPs that confer prote ...[more]

PMID: 29795138

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Project description:IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease closely related to the immune system. C1q is an important component of complement system. However, the correlation between C1q gene polymorphism and SLE has not been completely unified.AimThe primary aim of this meta-analysis was to examine the association between C1q polymorphisms and the risk of SLE.Material and methodsAll relevant articles were retrieved from PubMed, Web of Science and CNKI until June 2020. Pooled OR and 95% CI with random model were used to evaluate the strength of the association between C1q polymorphisms and SLE. Considering the limited number of studies, Trial Sequential Analysis (TSA) was applied to estimate whether the information was sufficient to make reliable and conclusive evidence. Both Egg's test and trim and fill method were performed to assess the publication bias.ResultsEight articles were included in this meta-analysis. The pooled results showed that C1q rs631090 was associated with SLE only in the homozygous and recessive model (allelic model: 1.169 (0.632-2.162), homozygous model: 2.342 (1.239-4.427), heterozygous model: 0.983 (0.395-2.448), dominant model: 1.036 (0.418-2.567), recessive model: 2.281 (1.227-4.239)) and there was no association between C1q rs172378 and rs292001 and SLE (rs172378 (allelic model: 1.071 (0.949-1.210), homozygous model: 1.172 (0.868-1.584), heterozygous model: 1.080 (0.892-1.306), dominant model: 1.100 (0.918-1.317), recessive model: 1.112 (0.863-1.431)); rs292001 (allelic model: 0.877 (0.657-1.170), homozygous model: 0.713 (0.320-1.589), heterozygous model: 0.714 (0.448-1.138), dominant model: 0.703 (0.414-1.196), recessive model: 0.927 (0.601-1.430)). Nevertheless, TSA showed that more information was needed to get more accurate results. There is no publication bias.ConclusionsThis meta-analysis suggested that C1q rs631090 but not rs172378 and rs292001 may be a potential susceptible factor associated with SLE. Nevertheless, due to the limited sample size in this meta-analysis, more large-scale association studies are still needed to confirm the results.

Project description:BackgroundEpidemiologic data suggest that patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer than women in the general population. In light of mechanistic studies suggesting that anti-DNA antibodies have anti-cancer effects, we sought to examine breast cancer risk in autoantibody strata in a well-characterized SLE cohort.MethodsSLE patients without a cancer diagnosis prior to entry in the Hopkins Lupus Cohort were studied (N = 2431). Overall and site-specific cancer incidence was calculated in racial strata and compared with the US Surveillance, Epidemiology and End Results (SEER) registry. Breast cancer incidence was further examined in autoantibody subsets. Patients were considered positive for an autoantibody if they were ever positive for a specificity during their disease course.ResultsPatients with SLE had a 37% lower risk of breast cancer (SIR 0.63, 95% CI 0.39-0.95). The risk of HPV-associated cancers (SIR 4.39, 95% CI 2.87-6.44) and thyroid cancer (SIR 2.27, 95% CI 1.04-4.30) was increased. Cancer risk varied by race, with breast cancer protection occurring in non-African Americans (SIR 0.29, 95% CI 0.11-0.63) and the increased risk of HPV-associated cancers occurring in African Americans (SIR 7.23, 95% CI 4.35-11.3). Breast cancer risk was decreased in patients ever positive for anti-dsDNA (SIR 0.55, 95% CI 0.29-0.96), anti-La (SIR 0.00, 95% CI 0.00-0.78), and lupus anticoagulant (SIR 0.37, 95% CI 0.10-0.94). Patients who were positive for fewer (0-2) SLE autoantibodies did not have a lower risk of breast cancer (SIR 0.84, 95% CI 0.47-1.39), but patients with 3+ autoantibodies had a 59% decreased risk (SIR 0.41, 95% CI 0.16-0.84).ConclusionsPositivity for multiple SLE autoantibodies was associated with a lower risk of breast cancer, supporting the hypothesis that a highly diversified immune response may exert an anti-cancer effect against some cancers. Validation of racial differences in cancer risk in SLE is required to determine whether cancer screening strategies should be targeted to racial subgroups.

Dataset Information

Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance.

Publications

Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance.

Similar Datasets

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