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TY - JOUR AU - Cucca, Francesco AU - Goy, Juliet V. AU - Kawaguchi, Yoshihiko AU - Esposito, Laura AU - Merriman, Marilyn E. AU - Wilson, Amanda J. AU - Cordell, Heather J. AU - Bain, Stephen C. AU - Todd, John A. PY - 1998 DA - 1998/07/01 TI - A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients JO - Nature Genetics SP - 301 EP - 302 VL - 19 IS - 3 AB - 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 ratio1. 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 cases2,3,4. 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' diabetes5,6,7,8,9,10,11,12,13. 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. SN - 1546-1718 UR - https://doi.org/10.1038/995 DO - 10.1038/995 ID - Cucca1998 ER -