Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21

In inflammatory bowel diseases (IBD), certain chromosomal candidate loci ha ve been repeatedly identified by independent studies in different populatio ns. To investigate the contribution of the loci on chromosomes 1, 3, 7, 12, 14, and 16 to the susceptibility of IBD in Finnish population, where the p redominant feature is the excess of ulcerative colitis (UC) families compar ed to Crohn's disease (CD) families, we carried out linkage analyses using 93 Finnish, multiply-affected IBD families. We observed nominal evidence fo r linkage to chromosome 3p21, consistent with earlier reports. The lod scor es peaked at D3S2432, with a maximum two-point lod score of 1.68 (p=0.0027) . In addition, we studied whether risk of IBD is associated with functional variants of two positional candidate genes; the chemokine receptor CCR5 ge ne on chromosome 3p21 and the interleukin-4 receptor a-subunit gene (IL4RA) on chromosome 16. We did not find any significant correlation between a 32 -bp deletion variant of CCR5 or a single nucleotide change A1902G (Gln576Ar g) of IL RA, and IBD phenotypes, with the exception that in the UC group ho mozygosity for the G1902 allele of IL4RA was less frequent (0.019 vs 0.049, P=0.038). In conclusion, our study, carried out in a genetically homogenou s population, suggests that chromosome 3 may contain a susceptibility gene for IBD.