title: Sex-related bias and exclusion mapping of the nonrecombinant portion of chromosome Y in human type 1 diabetes in the isolated founder population of Sardinia.
abstract: A male excess in Sardinian type 1 diabetic cases has previously been reported and was largely restricted to those patients carrying the HLA-DR3/nonDR4 genotype. In the present study, we have measured the male- to-female (M:F) ratio in a sample set of 542 newly collected, early-onset type 1 diabetic Sardinian patients. This data not only confirm the excess of male type 1 diabetic patients overall (M:F ratio = 1.3, P = 3.9 x 10(-3)) but also that the bias in male incidence is largely confined to patients with the DR3/nonDR4 genotype (M:F ratio = 1.6, P = 2.0 x 10(-4)). These sex effects could be due to a role for allelic variation of the Y chromosome in the susceptibility to type 1 diabetes, but to date this chromosome has not been evaluated in type 1 diabetes. We, therefore, established the frequencies of the various chromosome Y lineages and haplotypes in 325 Sardinian male patients, which included 180 cases with the DR3/nonDR4 genotype, and 366 Sardinian male control subjects. Our results do not support a significant involvement of the Y chromosome in DR3/nonDR4 type 1 diabetic cases nor in early-onset type 1 diabetes as a whole. Other explanations, such as X chromosome-linked inheritance, are thus required for the male bias in incidence in type 1 diabetes in Sardinia.
authors.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Microcitemico, Via Jenner, Cagliari 09121, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Contu
authors.forename: Laura
authors.initials: L
authors.lastname: Morelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zavattari
authors.forename: Rosanna
authors.initials: R
authors.lastname: Lampis
authors.forename: Efisio
authors.initials: E
authors.lastname: Angius
authors.forename: Paola
authors.initials: P
authors.lastname: Frongia
authors.forename: Daniela
authors.initials: D
authors.lastname: Murru
authors.forename: Mario
authors.initials: M
authors.lastname: Maioli
authors.forename: Paolo
authors.initials: P
authors.lastname: Francalacci
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Francesco
authors.initials: F
authors.lastname: Cucca
mesh_terms: D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D035061:Control Groups; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005838:Genotype; D015803:HLA-DR3 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007558:Italy; D008297:Male; D017678:Sex Distribution; D014998:Y Chromosome / Q000235:genetics*
chemical_list: D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen