title: Similar incidence of type 1 diabetes in two ethnically different populations (Italy and Slovenia) is sustained by similar HLA susceptible/protective haplotype frequencies.
abstract: The incidence of type 1 diabetes (T1DM) seems to depend in part on the population frequencies of susceptible and protective HLA haplotypes. The present study aimed to (i): characterize the genetic susceptibility to T1DM in the Slovenian population, (ii) test the general hypothesis that T1DM incidence is related to the frequencies of susceptible/protective haplotypes, (iii) compare allele, haplotype and genotype frequencies in Slovenians and Italians that represent two white populations with a similar incidence of T1DM (7.9/100,000/year and 8.1/100,000/year, respectively). The haplotype found most frequently among Slovenian T1DM patients was DRB1*0301-DQA1*0501-DQB1*0201 (53%). The DR4-DQA1*0301-DQB1*0302 haplotypes conferring susceptibility to T1DM were those bearing DRB1*0401 (OR = 12), DRB1*0404 (OR = 4.7) and DRB1*0402 (OR = 4.5). Negative associations with the disease were found for the following haplotypes: DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1301-DQA1*0102-DQB1*0603, DRB1*1101/1104-DQA1*0501-DQB1*0301, and DRB1*1401-DQA1*0101-DQB1*0503. Our findings indicate that the low frequencies of susceptible genotypes, in particular, DR3-DQA1*0501-DQB1*0201/DR4-DQA1*0301-DQB1*0302, together with a high frequency of protective haplotypes, could in part explain the low incidence of T1DM in the Slovenian population. The combined frequencies of susceptible genotypes were similar in the two populations (Slovenia = 19.2%, Italy = 17.6%), and the 95% confidence limits of the OR values for each genotype in the two populations overlapped, indicating no significant differences between the values. We conclude that the similar incidences of T1DM in Italian and Slovenian populations are in part a reflection of similar frequencies of HLA susceptible/protective haplotypes.
authors.affiliation: Endocrinologia, Dipartimento di Scienze Cliniche, University La Sapienza, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Petrone
authors.forename: T
authors.initials: T
authors.lastname: Battelino
authors.forename: C
authors.initials: C
authors.lastname: Krzisnik
authors.forename: T
authors.initials: T
authors.lastname: Bugawan
authors.forename: H
authors.initials: H
authors.lastname: Erlich
authors.forename: U
authors.initials: U
authors.lastname: Di Mario
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D012307:Risk Factors; D017524:Slovenia / Q000453:epidemiology
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C553505:HLA-DRB1*04:01 antigen; C553506:HLA-DRB1*04:02 antigen