Spondyloarthropathy, Susceptibility To, 3

For a phenotypic description and a discussion of genetic heterogeneity of spondyloarthropathy, see SPDA1 (106300).

Mapping

Laval et al. (2001) performed a genomewide scan on 185 families containing 255 sib pairs with ankylosing spondylitis (AS). Two-point and multipoint nonparametric linkage analysis identified suggestive linkage with the disease on chromosome 2q (lod scores, 1.6 and 2.5, respectively).

To identify major loci controlling clinical manifestations of AS, Brown et al. (2003) performed genomewide linkage analysis on 188 affected sib-pair families containing 454 affected individuals. Heritabilities of the traits studied were as follows: age at symptom onset, 0.33 (p = 0.005); disease activity assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 0.49 (p = 0.0001); and functional impairment assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI), 0.76 (p = 0.0000001). No linkage was observed between the MHC (see SPDA1, 106300) and any of the traits studied. Maximum linkage with the BASFI was seen at chromosome 2q (lod = 2.9), and significant or suggestive linkage between other traits and other chromosomal regions was observed. Brown et al. (2003) concluded that these clinical manifestations are largely determined by a small number of genes not encoded within the MHC.

Pursuant to the suggestive linkage of AS to chromosome 2q13 (Laval et al., 2001), a region containing the interleukin-1 (IL1; see 147760) family gene cluster, Timms et al. (2004) studied SNPs and haplotypes in the 2q13 region in 227 white British families containing affected sib pairs with AS, 317 parent-offspring trios with AS, and 200 healthy blood donors. They described strong association and transmission of SNPs and haplotypes in the IL1 family gene cluster with AS.

Gu et al. (2009) conducted a genomewide scan, followed by fine mapping analysis, on 75 individuals across multiple generations of 3 Han Chinese families with ankylosing spondylitis. Two of the pedigrees shared a 6-cM candidate region for AS on chromosome 2q36.1-q36.3 with a maximum heterogeneity lod score of 12.41 at marker D2S2228 (maximum lod score at that marker for each family individually was 3.26 and 2.13, respectively). The remaining family showed strong linkage to the HLA-B locus (see SPDA1, 106300).