Complement C1q and C2 polymorphisms are not risk factors for SLE in Indian Tamils

Abstract

Introduction

Complement system is an important effector component of the innate immune system. More than 30 plasma proteins undergo a cascade of enzymatic reactions to produce effector molecules to clear infectious microbes, immune complexes, post apoptotic cellular debris and thus participate in prevention of autoimmunity. Absolute deficiency of individual complement components and selective deficiency of classical pathway complement components are reported to be associated with severe infections and a high risk for lupus like syndromes. Genetic defects in gene encoding for complement components were reported to be associated with complement deficiency. This study was carried out to investigate whether C1q and C2 polymorphisms are risk factors for SLE in south Indian Tamils.

Materials and methods

Three hundred SLE patients fulfilling ACR criteria for SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls respectively. The genomic DNA obtained from both the groups was screened for two polymorphisms including a C/T transition in exon 2 of C1qA (rs121909581) by PCR-RFLP and a 28 bp deletion in sixth exon of C2 gene by PCR.

Results

C1q exon 2 C/T polymorphism analysis revealed that homozygous CC was the most common genotype in patients and controls. A single SLE patient was found to have heterozygous variant (CT). None of the patients or healthy controls were found to have 28 bp deletion variant of C2 gene.

Conclusion

The C/T polymorphism in exon 2 of C1qA and a 28 bp deletion in sixth exon of C2 gene were found to be rare in south Indian Tamil SLE patients. They do not appear to be susceptibility factors for SLE in Indian Tamils.

Introduction

Complement system of proteins, a multi-faceted effector component of the innate immune response, may contribute to the pathogenesis of SLE (Walport 2001a). In a normal individual more than 30 plasma proteins undergo a cascade of enzymatic reactions and produce effector molecules to clear infectious microbes, immune complexes and post apoptotic cellular debris, thus playing an important role in prevention of autoimmunity (Walport, 2001b, Chen et al., 2010). The coding region for C1q is localized on chromosome 1p^34–36 and consists of three genes, C1qA, C1qB and C1qC (Sellar et al. 1991). The genes for C2, C4A, C4B and factor B are located within the MHC class III region. Absolute deficiencies of individual and selective deficiency of classical pathway components are reported to be associated with severe infections and a high risk for development of lupus like syndrome (Gatenby, 1991, Botto, 1998, Botto et al., 1998, Bowness et al., 1994, Clemenceau et al., 1990, Fan et al., 1993, Lindqvist and Alarcon-Riquelme, 1999, Petri et al., 1993, Segurado et al., 1992, Sullivan et al., 1999, Traustadottir et al., 2002, Truedsson et al., 1993, Harley et al., 2008) This led to the ‘paradoxical hypothesis’ proposed by Walport et al. (Wilson 1994), according to which complement activation though primarily a pro-inflammatory immune mechanism, is actually anti-inflammatory during the development of certain types of autoimmunity. This may be attributed to the anti-inflammatory function of C1q, its ability to help solubilize immune complexes and aid in the clearance of apoptotic debris (Sontheimer et al. 2005). This process is defective in SLE patients (Donnelly et al. 2006). Thus defective immune complex clearance in active disease and inherited genetic variants, both may be possible causes of complement deficiency in these patients.

In Indians, SLE is reported to be severe with poor disease outcome (Malaviya et al. 1997) In this study, we have investigated whether C1q and C2 polymorphisms contribute to the risk of developing SLE in south Indian Tamils.