Single nucleotide polymorphisms in Intron 2 of the human interleukin-1 receptor antagonist (IL-1Ra) gene: further definition of the IL-1 beta and IL-1Ra polymorphisms in North American Caucasians and Taiwanese Chinese

Previous studies have suggested that a variable number tandem repeat (VNTR) polymorphism in the second intron of the interleukin-l receptor antagonist (IL-1Ra) gene and the single nucleotide polymorphisms at positions -511 an d +3954 of the IL-1 beta gene might be associated with increased risks of c hronic inflammatory diseases, autoimmune diseases and gastric cancer. In th e present study, IL-1 beta and IL-1Ra genotypes were analyzed among Asians in Taiwan and Caucasians in North America. We identified a novel polymorphi sm with 3 nucleotide substitutions in the IL-1Ra VNTR 2-repeat allele. One of the substitutions corresponds with the fourth 3' end nucleotide of the r everse primer that is often used for analysis of the IL-1Ra-associated VNTR locus. Mismatching between this primer and the 2-repeat allele can cause m isleading amplification results when stringent conditions are used for anne aling. The estimated haplotype frequencies of the variant IL-1 genes were s ignificantly different between Taiwanese and Caucasians. The frequency of t he pro-inflammatory IL-1Ra 2-repeat allele was significantly lower in Taiwa nese than in Caucasians. In contrast, the frequencies of the pro-inflammato ry IL-1 beta -511T allele and +3954C allele were significantly higher among Taiwanese compared with Caucasians.