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 and +3954 of the IL-1 beta gene might be associated with increased risks of chronic inflammatory diseases, autoimmune diseases and gastric cancer. In the present study, IL-1 beta and IL-1 Ra genotypes were analyzed among Asians in Taiwan and Caucasians in North America. We identified a novel polymorphism 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 reverse 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 misleading amplification results when stringent conditions are used for annealing. The estimated haplotype frequencies of the variant IL-1 genes were significantly different between Taiwanese and Caucasians. The frequency of the pro-inflammatory IL-1Ra 2- repeat allele was significantly lower in Taiwanese than in Caucasians. In contrast, the frequencies of the pro-inflammatory IL-1 beta -511T allele and +3954C allele were significantly higher among Taiwanese compared with Caucasians