Genetics of non-HLA marker genes in HLA-B27-positive and -negative ankylosing spondylitis families.
In families of HLA-B27+ ankylosing spondylitis (AS) patients, the occurrence of secondary cases of sacro-iliitis (SI) among B27+ first degree relatives is more than tenfold higher than expected from the population association of AS with HLA-B27. Secondary cases of SI also occur in relatives of HLA-B27- AS patients. We addressed the question whether other genetic factors than HLA-B27 played a role in the familial occurrence of AS and SI in B27+ and B27- AS cases. To this we tested 24 genetic marker systems including GM and PI in first degree relatives of AS patients: 118 first degree relatives with 16 secondary SI cases in families of 23 B27+ AS probands and 74 relatives with 6 secondary SI cases in families of 14 B27- AS probands. With a LIPED analysis we found no significant evidence for linkage for any of the markers tested, including HLA. In a co-segregation analysis we found a significant deviation from random segregation for HLA-B27 (p = 0.0005) and for HLA haplotypes (p = 0.052) to affected B27+ AS/SI siblings. No such deviation was found to B27- AS/SI cases. For GM and PI we found no significant cosegregation with AS/SI in B27+ and B27- families. In conclusion, apart from HLA-B27, we found no significant effect of any of the genetic marker systems tested in explaining the familial clustering of AS and SI among B27+ and B27- AS patients.
de Jongh
B M
BM
Department of Immunohaematology and Blood Bank, University Hospital, Leider, The Netherlands.
van der Linden
S M
SM
Volkers
W S
WS
Cats
A
A
D016000:Cluster Analysis; D005819:Genetic Markers; D015796:HLA-B27 Antigen / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D013167:Spondylitis, Ankylosing / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology
D005819:Genetic Markers; D015796:HLA-B27 Antigen