There is now considerable evidence that endometriosis is likely to be a complex multifactorial trait, such as diabetes or asthma, in which a number of susceptibility loci interact with each other, and the environment, to produce the disease phenotype. This thesis presents studies on the genetic and environmental basis of endometriosis in both a non-human primate model and in women. The study of the autopsy records of 399 female rhesus monkeys identified 81 (20%) with spontaneous endometriosis. Age, exposure to ≥ 3 oestradiol implants (relative risk 9.7, P < 0.001) or ≥ 1 hysterotomy (relative risk 5.8, P = 0.006) were significant risk factors as determined by conditional logistic regression. Living descendants of the affected animals had MRI scans which suggested that 8/113 (7%) had at least one endometriotic lesion >1 cm in diameter. Segregation analysis was conducted on the resulting 12 pedigrees, which contained 64 half sib-pairs, 2 full sibpairs and 11 mother-daughter pairs. Human, affected sib-pairs and families were recruited for the OXEGENE study to conduct sib-pair analysis using microsatellite markers at 10cM resolution across the entire genome. MRI studies of the first-degree relatives of women with rAFS stage III-IV disease estimated that the relative risk (λ_R) may be as high as 14 (95% Cl 4.8 - 30.3). Candidate gene studies, comparing the frequency of the GALT N314D polymorphism, the CYP1A1 MspI polymorphism and the GSTM1 and T1 null mutations in two case groups, with either sporadic disease or a family history of endometriosis, and two control groups, did not show evidence of association. Linkage analysis using three microsatellite markers and 50 affected sib-pairs in the region to which GSTM1 maps (1p13) did not show evidence of linkage to this region. However, there was an apparent relationship between the presence of both the GSTM1 null mutation and the CYP1A1 MspI polymorphism and an increased risk of endometriosis. The initial findings of a sib-pair analysis, using 29 microsatellite markers across chromosome one in 128 affected sib-pairs, did not reveal evidence of linkage. These findings provide some insight into the aetiology of endometriosis in women.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences