Inheritance of MHC class II genes in Lithuanian families with type 1 diabetes.

Type 1 diabetes mellitus (DM) is caused by genetic and environmental factors. Twice as many fathers as mothers of children with type 1 DM have the disease. The reason for the differences remains unclear. We looked at the transmission rates of diabetes-related alleles from parents to children with diabetes. All children with newly diagnosed type 1 DM from August 1, 1996 to August 1, 2000, aged 0 to 15 years, in Lithuania were invited to participate. Blood samples for full genetic analysis were available from 125 families. HLA DQA1, DQB1, and DRB1 typing was done on DNA extracted from peripheral blood, by polymerase chain reaction amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide probe 3'-end labeling with (32)P-dCTP, and hybridization, followed by stringency washes, autoradiography, and allele calling. Frequency of diabetes risk-related alleles DQB1*0302, DQA1*0201, DR4, and DR3 was less prevalent among Lithuanian than among Swedish children with type 1 DM. Transmission rates of DR4-DQB1*0302-DQA1*0301 and DR3-DQB1*0201-DQA1*0501 haplotypes from parents were higher than expected: chi(2) (TDT) 30.56, p < 0.0001, and chi(2) (TDT) 11.26, p = 0.0008, respectively. DQB1*0302 and DR4 were significantly more frequently transmitted from both parents, but DR3 was transmitted more frequently only from mothers. Any of these alleles had similar frequencies among female and male offspring. We conclude that, besides DR4-DQB1*0302-DQA1*0301 and DR3-DQB1*0201-DQA1*0501, there are other inherited alleles that determine risk for type 1 DM among children in Lithuania. Fathers might transfer other alleles of disease susceptibility in higher frequency or mothers might provide a protective environment during pregnancy, which results in higher risk to offspring of fathers than mothers to develop diabetes.