Interleukin-6 promoter polymorphisms (-174 G/C) in Malaysian patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves the inflammation of various organs upon deposition of immune complexes and is characterized by uncontrolled B cell hyperactivity. Despite intensive research on the etiology of the disease, the exact cause of the onset of SLE is unknown. The pathogenesis of the disease has been proposed to be associated with the imbalance of T helper type 1 (Th1) and Th2 cytokine activities. Elevated serum levels of interleukin-6 (IL-6), a Th2 cytokine with various functions in the regulation of human biological systems, are observed in SLE patients. In the present study, 100 Malaysian SLE patients and 100 controls were evaluated in order to determine the association of polymorphisms existing in the promoter region of the IL-6 gene with the onset of SLE. The homozygous G genotype was found to be significant in SLE patients (χ 2 = 33.754; P = 0.00000000625), whereas the heterozygous G/C genotype was significant in the controls (χ 2 = 25.087; P = 0.000000548). We suggest that the C allele might have a masking effect on the G allele when both alleles are present in heterozygous individuals. However, we did not observe any significant association of the homozygous C allele with the onset of SLE or with protection from the disease (χ 2 = 1.684; P = 0.194366).

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.…”

Lack of association between Gly82Ser, 1704G/T and 2184A/G of RAGE gene polymorphisms and retinopathy susceptibility in Malaysian diabetic patients

“…Forward primer 5'-GGA GCC AGA AGG TGG AGC AGT AG-3' and reverse primer 5'-GTC TCA CCG ATG ATG CTG ATG ATG-3' were used to amplify the intron 7 region containing 1704G/T (rs184003) polymorphism, whereas 2184A/G (rs3134940) polymorphism in the intron 8 region was amplified by forward primer 5'-GGC CTC AGG ACC AGG GAA CCT ACA-3' and reverse primer 5'-TTG GTC AGG CTG GTC TCG AAC TCC-3'. All amplifications were performed in a final volume of 20 mL containing 100 ng genomic DNA and appropriate PCR mixture, as previously described (Chua et al, 2009). Following that, PCR was performed in a thermal cycler according to the conditions described by Chua et al (2010).…”

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.…”