A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients.
Nat Genet
; 19(3): 301-2, 1998 Jul.
Article
em En
| MEDLINE
| ID: mdl-9662410
ABSTRACT
It is generally assumed that the malefemale (MF) 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 MF ratio and low incidence ones (Asian and African) have a low MF ratio. We have now analysed the MF 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 not = DR4) with a MF ratio of 1.7 (P=9.3x10(-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=2.7x10(-4); single point MLS=4.5, P=2.7x10(-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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomo X
/
Antígeno HLA-DR3
/
Diabetes Mellitus Tipo 1
/
Ligação Genética
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Reino Unido