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- Title
A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients.
- Authors
Cucca, Francesco; Goy, Juliet V.; Kawaguchi, Yoshihiko; Esposito, Laura; Merriman, Marilyn E.; Wilson, Amanda J.; Cordell, Heather J.; Bain, Stephen C.; Todd, John A.
- Abstract
It is generally assumed that the male:female (M:F) ratio in patients with type 1 (insulin-dependent) diabetes mellitus (IDDM) is 1. A recent survey, however, revealed that high incidence countries (mainly European) have a high M:F ratio and low incidence ones (Asian and African) have a low M:F ratio. We have now analysed the M:F ratio according to genotype at the major locus, the major histocompatibility complex (MHC; IDDM1). There are two main IDDM1 susceptibility haplotypes, HLA-DR3 and -DR4, which are present in 95% of Caucasian cases. We report here that in medium/high incidence Caucasian populations from the United States of America, United Kingdom and Sardinia (1307 cases), the bias in male incidence is largely restricted to the DR3/X category of patients (X ≠ DR4) with a M:F ratio of 1.7 (P = 9.3 × 10?7), compared with a ratio of 1.0 in the DR4/Y category (Y ≠ DR3). This is additional evidence for significant heterogeneity between the aetiology of 'DR4-associated' and 'DR3-associated' diabetes. We analysed linkage of type 1 diabetes to chromosome X, and as expected, most of the linkage to Xp13?p11 was in the DR3/X affected sibpair families (n = 97; peak multipoint MLS at DXS1068 = 3.5, P = 2.7 × 10?4; single point MLS = 4.5, P = 2.7 × 10?5). This is evidence for aetiological heterogeneity at the IDDM1/MHC locus and, therefore, in the search for non-MHC loci in type 1 diabetes, conditioning of linkage data by HLA type is advised.
- Subjects
DIABETES; SEX differences (Biology)
- Publication
Nature Genetics, 1998, Vol 19, Issue 3, p301
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/995