Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients

The promoter polymorphisms of tumour necrosis factor-alpha (TNF-alpha) and intronic Lymphotoxin-alpha (LT alpha) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-alpha (-308G/A; 238G/A) and LT alpha (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-alpha 308A (OR = 2.3, p = 0.0001, Pc = 0.0003) and LT alpha +252G (OR = 2.1, p < 0.0001, Pc < 0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR = 12.2, p = 0.0050). Serum levels of TNF-alpha and LT alpha also were found to be significantly higher in patients showing variant alleles. TNF-alpha 308G/A + A/A genotypes (p < 0.01) and LT alpha +252 A/G + G/G genotypes (p < 0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with 308G/A + A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR = 3.9, p = 0.0014, Pc = 0.0098) and anti-Sm antibodies (OR = 4.1, p = 0.0002, Pc = 0.0014). The present study suggests TNF-alpha 308A and LT alpha +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-alpha and LT alpha and concomitant discrete clinical features among Indian SLE patients. (C) 2016 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.