Back to Search
Start Over
LADA and T1D in Estonian population — Two different genetic risk profiles
- Source :
- Gene. 497:285-291
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Aims/hypothesis The aim of our study was to analyze combined impact of 17 polymorphisms at 8 gene regions previously shown to be associated with autoimmunity in diabetes. We hypothesized that the genetic predisposition is multiplicative and joint risk of different diabetic phenotypes forms by distinct combination of susceptibility loci. Methods An ethnically homogenous population of Estonian origin, including 65 LADA patients, 154 patients with T1D, 260 patients with T2D and 229 non-diabetic controls, was genotyped for polymorphisms/haplotypes in HLA-DQB1, insulin gene (rs689, rs3842729), PHTF1–PTPN22 region (rs2476601, rs6679677), CTLA4 region (rs231806, rs16840252, rs5742909, rs231775, rs3087243, rs2033171), ICOS region (rs10932037, rs4675379), CD25 (rs706778), CD226(rs763361), NAA25 (rs17696736). Results As expected, the risk of T1D was consistently attributed by HLA-DQB1 haplotypes, but also by haplotypes of INS and PHTF1–PTPN22 region, and rs17696736 in NAA25. By contrast, LADA was associated only with T1D-protective HLA haplotypes and with two more frequent haplotypes of the CTLA4. It is of interest, that seldom CT haplotype of PHTF1–PTPN22 region carried the risk for autoantibody-negative T2D. The final best-fitted model for T1D genetic risk contained six gene regions (HLA-DQB1, INS, PHTF1, CTLA4 + 49, CD226 and NAA25) and for LADA only two (HLA-DQB1 and CTLA4 + 49). The AUCs of these models are 0.869 and 0.693, respectively. Conclusions Classical T1D-risk haplotypes of HLA and some non-HLA loci describe quite well the genetic risk for T1D but not for LADA. The need of further studies should be stressed to discover the real risk factors for slower forms of autoimmune diabetes in adults.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Male
endocrine system diseases
CD226
immune system diseases
HLA-DQ beta-Chains
Insulin
CTLA-4 Antigen
Age of Onset
N-Terminal Acetyltransferase B
Genetics
education.field_of_study
General Medicine
Middle Aged
Phenotype
Female
Adult
Estonia
Risk
Population
Human leukocyte antigen
Biology
White People
Evolution, Molecular
Inducible T-Cell Co-Stimulator Protein
Young Adult
Acetyltransferases
Diabetes mellitus
Genetic predisposition
medicine
Humans
SNP
Genetic Predisposition to Disease
education
Gene
Alleles
Homeodomain Proteins
Polymorphism, Genetic
Haplotype
Interleukin-2 Receptor alpha Subunit
nutritional and metabolic diseases
Protein Tyrosine Phosphatase, Non-Receptor Type 22
medicine.disease
Diabetes Mellitus, Type 1
Genetics, Population
Diabetes Mellitus, Type 2
Haplotypes
Genetic Loci
Transcription Factors
Subjects
Details
- ISSN :
- 03781119
- Volume :
- 497
- Database :
- OpenAIRE
- Journal :
- Gene
- Accession number :
- edsair.doi.dedup.....5d5fdf7563e92fd7d07ad34e9b190f60