Background/Purpose:

There are few studies of the heritability of ankylosing spondylitis (AS) in families, a disease where hereditary factors play a dominant role in disease pathogenesis. One study (Calin et al, Lancet 1999; 354: 1687-90) showed that in families with affected parent: offspring pairs, the mother was more likely to be affected compared to the father. This study aims to better understand the pattern of inheritance of this disease in familial AS and to determine whether exists gender bias in disease inheritance in parent: offspring pairs in familial AS.

Methods:

Two cohorts were examined comprising 105 affected parent:offspring pairs, including one taken from 865 AS patients meeting modified New York Criteria enrolled in a longitudinal study of outcome who were administered a questionnaire querying spondyloarthritis symptoms in their first degree relatives (the proband recall cohort) and a second from 210 AS probands enrolled in a study of familial AS genetics, where the diagnoses were confirmed by either review of pelvic radiographs of affected family members or by radiographic reports thereof (the radiographic cohort). We tested whether the proportion of affected fathers was same as that of affected mothers and also evaluated the gender association between affected parents and offspring by conducting a test of one sample proportion and Chi-square test, respectively, at a 5% level of significance. All parent:offspring pairs were HLA-B27 positive.

Results: Overall, in 105 parent:offspring pairs, the father was the more likely affected parent after combining the parent: offspring pairs from the proband recall and the radiographic cohorts (p = 0.003). In the proband recall cohort there were 54 parent:offspring pairs and the father was more likely to be the affected parent compared to the mother (p = 0.007). In the radiographic cohort there were 51 affected parent: offspring pairs. Here a trend was also seen for greater paternal involvement, although the results were not statistically significant (p = 0.12).

Next it was tested whether affected parents are more likely to transmit the disease to their same or opposite gender offspring. In the radiographic cohort, the father and son were affected in 26 of 55 (47%) of father:offspring pairs whereas there in an affected mother:son pair in 12 of 24 (50%) of mother:offspring pairs (p = 0.40). Similar results were seen in the proband recall cohort-28/36 (77%) father:son versus 12/17 (71%) affected mother:son pairs, or in the combined cohorts (p = 0.07). Overall, sons were more likely to be affected than daughters (p = 0.0003) in the proband recall and combined cohorts.

Conclusion: In affected parent:offspring pairs with AS, the father is more likely to be affected than the mother, and there is greater likelihood for transmission to male versus female offspring, perhaps reflecting the male gender bias known to exist in this disease. There were no significant differences in parental transmission AS to same gender versus opposite gender offspring.