Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus

Racila, Doina; Sontheimer, Clayton; Sheffield, A; Wisnieski, Jeffrey J.; Racila, Emil; Sontheimer, Richard D.

doi:10.1191/0961203303lu329oa

Cited by 79 publications

(67 citation statements)

References 31 publications

(27 reference statements)

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“…The A allele of C1QA polymorphism rs172378 has been associated with decreased complement activity, resulting in reduced metastasis associated with breast cancer (Petry and Loos, 2005;Racila et al, 2006). The decrease in complement activity is suggested to result in less clearance of apoptotic tumour cells (Racila et al, 2003), and in a more effective antibody response against the tumour. Also, this same allele has been reported to associate with lower levels of serum C1qA protein (Racila et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…The decrease in complement activity is suggested to result in less clearance of apoptotic tumour cells (Racila et al, 2003), and in a more effective antibody response against the tumour. Also, this same allele has been reported to associate with lower levels of serum C1qA protein (Racila et al, 2003). Therefore, we hypothesised that the A allele, or another allele in tight linkage disequilibrium, could have a regulatory role and could correlate with lower expression of C1qA.…”

Section: Discussionmentioning

confidence: 99%

“…The SNP rs172378 has been previously reported to have a correlation with lower levels of C1qA in serum (Racila et al, 2003). We analysed the correlation of total levels of C1QA and the rs172378 genotype in the blood of control individuals ( Figure 1A).…”

Section: Gene Expression Analysis Of C1qa (Rs172378)mentioning

confidence: 99%

“…Racila et al (2006) have also reported that rs172378 correlates with decreased complement activity, which then reduces the instance of metastasis associated with breast cancer, perhaps by resulting in an inefficient clearance of apoptotic tumour cancer cells, which consequently results in the development of a more effective antibody response against the tumour. The same group previously identified a correlation between the A allele of rs172378 with lower expression of the C1QA protein (Racila et al, 2003). The purpose of this study was to investigate the association of this SNP with expression of C1QA and breast cancer survival.…”

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confidence: 92%

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Common germ-line polymorphism of C1QA and breast cancer survival

et al. 2010

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BACKGROUND: A synonymous single nucleotide polymorphism (SNP) rs172378 (A4G, GlyÀ4Gly) in the complement component C1QA has been proposed to be associated with distant breast cancer metastasis. We previously reported overexpression of this gene to be significantly associated with better prognosis in oestrogen-receptor-negative tumours. The purpose of this study was to investigate the association of rs172378 with expression of C1QA and breast cancer survival. METHODS: We analysed the gene expression pattern of rs172378 in normal and tumour tissue samples, and further explored its involvement in relation to mortality in 2270 women with breast cancer participating in Studies of Epidemiology and Risk factors in Cancer Heredity, a population-based case -control study. RESULTS: We found that although rs172378 showed differential allelic expression significantly different between normal (preferentially expressing the G allele) and tumour tissue samples (preferentially expressing the A allele), there was no significant difference in survival by rs172378 genotype (per allele hazard ratio (HR) 1.02, 95% CI: 0.88 -1.19, P ¼ 0.78 for all-cause mortality; HR 1.03, 95% CI: 0.87 -1.22, P ¼ 0.72 for breast-cancer-specific mortality). CONCLUSION: Our study results show that rs172378 is linked to a cis-regulatory element affecting gene expression and that allelic preferential expression is altered in tumour samples, but do not support an association between genetic variation in C1QA and breast cancer survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Gene Expression Analysis Of C1qa (Rs172378)mentioning

confidence: 99%

mentioning

confidence: 92%

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Common germ-line polymorphism of C1QA and breast cancer survival

et al. 2010

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“…The complement proteins C1q, C3 and C4 are deposited at the site of inflammation in the kidney and play an important role in the pathogenesis of LN. It is well known that hereditary C1q deficiency is strongly related to SLE, but there are several and inconsistent studies exploring single nucleotide poly-morphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE (1)(2)(3)(4)(5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

The GG rs292001 genotype prevails in seronegative for ANA and anti-dsDNA antibodies patients with lupus nephritis

Radanova

Bratoeva

Nazifova-Tasinova

et al. 2016

SSM

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Rs292001 is single nucleotide polymorphism in non-coding regions of the C1QA gene. C1q is a subcomponent of the C1 first component of the classical pathway of complement activation. Rs292001 was investigated for an association with some conventional immunological markers of lupus nephritis (LN) activity in systemic lupus erythematosus (SLE) patients -levels of C1q, C3, C4, anti-C1q, anti-nuclear (ANA) and anti-ds-DNA autoantibodies.Genomic DNA was isolated from peripheral blood of 18 patients with biopsy-proven LN. SNP genotyping for the presence of rs292001 was performed by quantitative real-time PCR method. Presence of complement C1q, C3 and C4 and anti-C1q autoantibodies was screened by ELISA. ANA and anti-dsDNA antibodies were detected by double immunodiffusion assays and indirect immunofluorescence.We found that the GG rs292001 genotype prevailed in seronegative for ANA and anti-dsDNA antibodies LN patients (p=0.008; p<0.012). The AA rs292001 genotype showed a trend towards lower serum C1q levels.These results reaffirm a previously established probable protective role of the G allele against the clinical activity of the SLE.

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Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91 pathway in systemic lupus erythematosus

Donnelly¹,

Roake²,

Brown³

et al. 2006

Arthritis & Rheumatism

120

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Objective. A deficiency in a subcomponent of C1q can result in increased susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE). The monocyte endocytic receptor CD91 is implicated in the endocytosis of apoptotic neutrophils via interactions with C1q and calreticulin. In this clinical study, we studied the binding of C1q to leukocytes and determined whether C1q bound specifically to calreticulin and CD91 on cells undergoing apoptosis in SLE.Methods. Proximal antibody phage display, calreticulin-transfected cells, and immunocytochemical and confocal techniques were used in a comprehensive analysis of direct binding of C1q to apoptotic neutrophils that were obtained from healthy individuals and from patients with SLE. In addition, apoptotic cellular systems were assessed in vitro.Results. C1q appeared to colocalize to apoptotic blebs on the surface of leukocytes in association with both calreticulin and CD91, as determined by phage display and transfected cell studies. However, C1q did not bind to apoptotic cells isolated from SLE patients, despite the positivity of the cells for both calreticulin and CD91. Surface expression of calreticulin decreased on neutrophils as they aged, but increased on monocytes. In an apoptotic phagocytic assay, the addition of C1q and calreticulin significantly enhanced the phagocytosis of apoptotic cell debris by monocyte-derived cells.Conclusion. These observations indicate that neutrophils from SLE patients have a reduced ability to be recognized and removed by the C1q/calreticulin/CD91-mediated apoptotic pathway, despite the presence of main apoptotic recognition partners. This suggests that an additional component, as yet unidentified, acts as a C1q binding partner on apoptotic cells, and this component may be lacking in cells isolated from SLE patients.

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Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus

Cited by 79 publications

References 31 publications

Common germ-line polymorphism of C1QA and breast cancer survival

Common germ-line polymorphism of C1QA and breast cancer survival

The GG rs292001 genotype prevails in seronegative for ANA and anti-dsDNA antibodies patients with lupus nephritis

Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91 pathway in systemic lupus erythematosus

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