title: Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21.
abstract: In inflammatory bowel diseases (IBD), certain chromosomal candidate loci have been repeatedly identified by independent studies in different populations. 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 predominant feature is the excess of ulcerative colitis (UC) families compared to Crohn's disease (CD) families, we carried out linkage analyses using 93 Finnish, multiply-affected IBD families. We observed nominal evidence for linkage to chromosome 3p21, consistent with earlier reports. The lod scores 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 gene on chromosome 3p21 and the interleukin-4 receptor alpha-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 (Gln576Arg) of IL4RA, and IBD phenotypes, with the exception that in the UC group homozygosity 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 homogenous population, suggests that chromosome 3 may contain a susceptibility gene for IBD.
authors.affiliation: Department of Medicine, Helsinki University Hospital, Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Paavola
authors.forename: T
authors.initials: T
authors.lastname: Heliö
authors.forename: M
authors.initials: M
authors.lastname: Kiuru
authors.forename: L
authors.initials: L
authors.lastname: Halme
authors.forename: U
authors.initials: U
authors.lastname: Turunen
authors.forename: J
authors.initials: J
authors.lastname: Terwilliger
authors.forename: A L
authors.initials: AL
authors.lastname: Karvonen
authors.forename: R
authors.initials: R
authors.lastname: Julkunen
authors.forename: S
authors.initials: S
authors.lastname: Niemelä
authors.forename: H
authors.initials: H
authors.lastname: Nurmi
authors.forename: M
authors.initials: M
authors.lastname: Färkkilä
authors.forename: K
authors.initials: K
authors.lastname: Kontula
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005387:Finland; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000208:ethnology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*
chemical_list: D019713:Receptors, CCR5; D019948:Receptors, Interleukin-4