PCR-RFLP Genotyping of C1q Mutations and Single Nucleotide Polymorphisms in Malaysian Patients with Systemic Lupus Erythematosus

Abstract

Five types of known mutations within the C1q gene [located at C1qA-Gln186 (C >T), C1qB-Gly15 (G >A), C1qB-Arg150 (C >T), C1qC-Gly6 (G >A), and C1qC-Arg41 (C >T)] and two SNPs located at C1qA-Gly70 (G/A) and C1qC-Pro14 (T/C) were screened in a multiracial Malaysian population. One hundred thirty patients with systemic lupus erythematosus (SLE) and 130 matched healthy control subjects were genotyped using PCR-RFLP methods. We found no occurrence of the five types of mutations in either the homozygous or heterozygous form among the 260 samples studied. Statistical analysis also revealed that there were no significant associations observed in the genotype distributions and allele frequencies among the patients with SLE and healthy control subjects with both C1qA-Gly70 (G/A) and C1qC-Pro14 (T/C) SNPs. Overall, C1q deficiency was not proven as a primary causative genetic predisposition factor for SLE in the Malaysian population.

Lack of association between RANTES-28, SDF-1 gene polymorphisms and systemic lupus erythematosus in the Malaysian population

“…To the best of our knowledge, this is the first study relating these SNPs to susceptibility for SLE in Malaysia. Other studies based on complement components, interleukins and lymphocyte antigen also failed to demonstrate any significant correlations (Puah et al, 2007;Chew et al, 2008;Chua et al, 2009aChua et al, ,b, 2010. Onset of SLE might be a result of interaction and involvement of various factors and genes.…”

C1qrs292001 polymorphism and C1q antibodies in juvenile lupus and their relation to lupus nephritis

“…In contrast, the C1q rs292001 SNP was not associated with the risk of SLE in the Polish population [33], LN risk in the Bulgarian population, despite the trend towards lower C1q levels [13], and risk of schizophrenia in the Armenian population [34]. Conversely, C1q rs172378 and rs15940 showed no significant association with SLE, and C1q deficiency was not proved as a primary causative genetic predisposition factor for SLE in the Malaysian population [16]. The controversial results observed between various reports may be due to different disease phenotype (systemic, cutaneous, renal), different age (adult versus juvenile as in the present work), extensive geographic variations between different studied populations, different sample size (as low as 38 LN patients to 800 SLE patients), different typing techniques (such as RFLP, real-time PCR), possibly study designs and differences in ethnic backgrounds (Caucasian, Asian, European and Arabic).…”

“…A hierarchical grade of susceptibility exists in which 93, 75, $10, 13 and > 5% of individuals, respectively, will develop lupus-like illness if they are deficient in C1q, C4, C2, C3 or C5-9 [27]. The rarity of these genetic deficiencies has led to further sequence analysis of the A, B and C chains of C1q to identify single nucleotide polymorphisms (SNP) that may account for defective C1q function, C1q antigenicity or decreased concentration in the serum of SLE sufferers [8,10,11,[13][14][15][16][28][29][30].…”

Angiotensin-converting enzyme gene I/D dimorphism does not play a major role in the susceptibility of Malaysian systemic lupus erythematosus patients

“…Some of the important target genes such as C4, C1q, CTLA-4, IL-6, IL-1, RANTES-28, and SDF-1 have been studied previously in the Malaysian population (Puah et al, 2007;Chew et al, 2008;Chua et al, 2009aChua et al, ,b, 2010Lian et al, 2011); however, most of them were found to have no major significant association with SLE susceptibility. Hence in this study, we aimed to target and investigate the distribution of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) dimorphism and its potential association to the susceptibility of SLE.…”