HLA class II alleles and haplotypes in Lithuanian children with type 1 diabetes and healthy children (HLA and type 1 diabetes).
OBJECTIVE
Type 1 diabetes mellitus is a slowly progressive autoimmune disease. The genetic background of type 1 diabetes mellitus is polygenic with the major disease locus located in the human leukocytes antigen (HLA) region. High risk and protective alleles, haplotypes, and genotypes have been determined in Lithuanian children with type 1 diabetes mellitus and healthy children.


METHODS
In this case-control study, 124 children with diabetes (55 males and 69 females; mean age, 9.2±3.9 years) were tested for HLA class II and compared with 78 healthy controls (43 males and 35 females; mean age, 10.8±3.4 years; range, 0-15 years). HLA DRB1, DQA1, and DQB1 alleles were genotyped using a polymerase chain reaction.


RESULTS
T1D risk-associated haplotypes (DR4)-DQA1*0301-DQB1*0302, (DR3)-DQA1*0501-DQB1*0201, and (DR1)-DQA1*0101-04-DQB1*0501 were more prevalent among children with diabetes than controls (50.0%, 41.1%, and 37.9% vs. 10.3%, 5.1%, and 24.4%, P<0.001). The haplotypes (DR4)-DQA1*0301-DQB1*0302 and (DR3)-DQA1*0501-DQB1*0201 increased T1D risk by 8.75 and 12.93 times, respectively (P<0.001). Protective haplotypes (DR2)-DQA1*0102-B1*0602, (DR11/12/13)-DQA1*05-DQB1*0301, and (DR13)-DQA1*0103-DQB1*0603 were significantly more prevalent among controls than children with diabetes (25.6%, 33.3%, 19.2% vs. 0%, 3.2%, 0%; P<0.001). These frequencies are quite similar to those from neighbor countries with varying incidence of type 1 diabetes mellitus.


CONCLUSIONS
HLA class II haplotypes associated with type 1 diabetes mellitus positively or negatively were the same in Lithuanian children as in other European Caucasian populations. Differences in incidence and clinical manifestations of type 1 diabetes might be due to different environmental factors and/or lifestyle.
Department of Preventive Medicine, Institute of Endocrinology, Kaunas University of Medicine, Eivenių 2, 50028 Kaunas, Lithuania. Erika.S@takas.lt
Erika
E
Skrodenienė
Dalia
D
Marčiulionytė
Zilvinas
Z
Padaiga
Edita
E
Jašinskienė
Vaiva
V
Sadauskaitė-Kuehne
Carani B
CB
Sanjeevi
Johnny
J
Ludvigsson
D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008019:Life Style; D008097:Lithuania / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D018709:Statistics, Nonparametric
D006680:HLA Antigens