Genetic prediction of type 1 diabetes in a population with low frequency of HLA risk genotypes and low incidence of the disease (the DIABFIN study).

To develop a sensitive, specific screening strategy for predicting genetic risk for type 1 diabetes mellitus (T1DM) in the low-incidence continental Italian population, and to define with this tool, a cohort of high-to-moderate risk infants for an immunological follow-up study aimed at identifying environmental risk factors for T1DM. 4855 newborns in three regions of continental Italy were screened for T1DM HLA-DRB1-DQB1 risk genotypes using a reverse line blot typing method. Risk classification was based on odds ratios (OR) found in a preliminary case-control study (356 T1DM patients, 412 controls). Screening efficiency was optimized by allele subtyping. Screening for well-known T1DM susceptibility genotypes [DRB1*03/*04-DQB1*0302; DRB1*03/*03; DRB1*04/*04-DQB1*0302; DRB1*04-DQB1*0302/X where X is not equal to DRB1*03, DRB1*04-DQB1*0302, DQB1*0602 or DQB1*0603] was associated with <60% sensitivity due to their low frequencies in the general Italian population. Inclusion of an additional genotype from which protective DRB1 and DQB1 alleles had been excluded [DRB1*03/X degrees where DQB1 is not equal to *0301, *0503, *0602, or *0603 and X degrees not equal DRB1*03, DRB1*04-DQB1*0302 or DRB1*07] increased screening sensitivity to 75% (specificity: 85%). Among 4855 newborns, we have found the high-risk genotype [DRB1*03/*04-DQB1*0302; estimated absolute risk (AR) 1/23] to be present in only 0.9%. The moderate-risk genotypes were found in 13.8% of newborns (estimated AR 1/177). Risk classification must be tailored to the characteristics of the individual population, in particular, the allelic frequencies in the background population and T1DM prevalence. We have developed a screening strategy with good levels of sensitivity that should prove effective for use throughout the Italian peninsula.

Buzzetti R ，Galgani A ，Petrone A ，Del Buono ML ，Erlich HA ，Bugawan TL ，Lorini R ，Meschi F ，Multari G ，Pozzilli P ，Locatelli M ，Bottazzo G ，Di Mario U ... -  《DIABETES-METABOLISM RESEARCH AND REVIEWS》

[Predictive genetic screening for type-1 diabetes in the Hungarian population].

Hermann R ，Soltész G 《ORVOSI HETILAP》

HLA class II typing in newborns reveals a low frequency of the DRB1*04 allele and a high frequency of DRB1*11 allele in three regions of continental Italy.

Galgani A ，Petrone A ，Spoletini M ，Hodge A ，Del Buono ML ，Locatelli M ，Buzzetti R ，Diabfin Study Group ... -  《HUMAN IMMUNOLOGY》

HLA DRB1, DQB1 and insulin promoter VNTR polymorphisms: interactions and the association with adult-onset diabetes mellitus in Czech patients.

Cejkova P ，Novota P ，Cerna M ，Kolostova K ，Novakova D ，Kucera P ，Novak J ，Andel M ，Weber P ，Zdarsky E ... -  《-》

Genetic and diabetic auto-antibody markers in Saudi children with type 1 diabetes.

Human leukocyte antigen DRB1 and DQB1 contribute to the genetic susceptibility of type 1 diabetes (T1DM), and they are involved in the induction of the autoimmune destruction of pancreatic beta cells precipitating the disease. The objective of this study was to examine diabetic auto-antibodies (ICA-512, GAD65) and the HLA-DR/DQ genotype among T1DM Saudi children in a cross-sectional study conducted at King Khalid University and National Guard Hospitals, Riyadh. Subjects included in this study were 103 Saudi patients and 180 healthy controls. In all, 41% of patients were positive for ICA512 73.3% positive for GAD65, and 27.3% had both antibodies. The risk alleles were DRB1*0301 (odds ratio [OR] = 11.1); DRB1*0405 (OR = 6.02); DRB1*0401 (OR = 5.8); DQB1*0201 (OR, 17.69) and DQB1*0302 (OR = 3.77). In addition, the DRB1*03/04-DQB1*02/0302 (OR = 123.4) is positively associated with T1DM. However, DRB1*0403 (OR = 0.27), DRB1*1101 (OR = 0.049), DRB1*1307 (OR = 0.28), DRB1*1501 (OR = 0.12), DQB1*0301 (OR = 0.03), DQB1*0401 (OR = 0.04), and DQB1*0602 (OR = 0.16) were protective. Among GAD-positive patients, 81% were DRB1*0301, 68.75% were DQB1*0201, 62.5% were DRB1*0405, 43.75% were DQB1*0302, and 43.7% were DRB1*03/04. Among ICA512-positive patients, all were DRB1*0301, 66.6% were DQB1*0201, 55% were DRB1*0405, 33.3% were DQB1*0302, and 55% were DRB1*03/04. In conclusion, these results show a strong association of HLA-DQB1*0201/0302 and DRB1*03/04 with T1DM. Thus, combining genetic markers with autoantibody is useful in a screening program for early detection of T1DM among Saudi children.

Manan H ，Angham AM ，Sitelbanat A 《-》