Single Nucleotide Polymorphisms in <i>TNF-</i> α, <i>TNFR2</i> Gene and TNF-α Production in Asian Indians

Abstract

Polymorphisms in the TNF-alpha and TNF receptor type 2 (TNFR2) genes in Asian Indians are not well understood. We investigated single nucleotide polymorphisms in the TNF-alpha 5'-flanking promoter/enhancer region and in exons 6, 9 and 10 of TNFR2 gene by PCR-restriction length polymorphism (PCR-RFLP) and PCR-sequence specific primer (SSP) techniques, respectively. The results showed single bi-allelic polymorphism in TNF-alpha (-308G > A) and in TNFR2 exons 6 (676 T > G) and 9 (1176 G > A). Additionally, three bi-allelic polymorphisms (1663 G > A, 1668G > T and 1690C > T) were observed in the exon 10 of TNFR2 gene. The distribution of polymorphic alleles distinctly differed in Aryan and Dravidian Indian communities. The TNF-alpha and TNFR2 genotype and allele frequencies of Asian Indians stand closer to other Asian populations but distant from Caucasians. Furthermore, TNF-alpha -308 GA genotype was associated with significantly higher production of TNF-alpha as compared to GG genotype. These polymorphisms may be related to variation in TNF-alpha and TNFR2 expression during immune response to various stimuli in Asian Indians.