Distribution of insulin‐dependent diabetes mellitus (IDDM)‐related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region

Nejentsev, S; Koskinen, Suvi; Sjöroos, Minna; Reijonen, Helena; Schwartz, E.I.; Kovalchuk, L.; Sochnev, A.; Adojaan, Bela; Podar, T; Knip, Mikael; Simell, Olli; Koskenvuo, Markku; Åkerblom, Hans K.; Ilonen, Jorma

doi:10.1111/j.1399-0039.1998.tb03074.x

Cited by 36 publications

(31 citation statements)

References 12 publications

(7 reference statements)

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“…In this respect, it is interesting to note that when comparing the frequencies of the HLA DR3-DQ2/DR4-DQ8 genotype in patients with T1D in Europe, we observed that this high risk genotype was more prevalent in patients from countries with a low disease incidence suggesting that these populations are at an earlier stage of the natural evolution of diabetes history [15,16]. The declining protective efficiency of DQB1*0603 is reflected in fact in the behaviour of the DQB1*0302/DQB1*0603 genotype which was increased among patients diagnosed during the later time period and we observed this particular genotype to be associated with T1D in Finland, whereas in several other populations with lower diabetes incidence no such disease association has been detected [17].…”

Section: Discussionmentioning

confidence: 97%

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

et al. 2003

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Aims/hypothesis. The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000 in Finland -a general trend seen in almost all developed countries that can only be explained by environmental factors. The aim of this study was to test the possible effect of a changing environment on distribution of genotypes associated with disease susceptibility. Methods. HLA DRB1-DQA1-DQB1 genes and two diabetes-associated polymorphisms at IDDM2 and IDDM12 were analyzed. The frequencies of genotypes were compared between cases diagnosed with childhood-onset Type 1 diabetes during the period of 1939-1965 (n=367) and those diagnosed between 1990 and 2001 (n=736). Chi-square statistics or the Fisher's Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups.

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Section: Discussionmentioning

confidence: 97%

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

et al. 2003

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“…A significant contribution to type 1 diabetes genetic susceptibility appears to be encoded by the HLA DQB1 locus and in particular by DQB1*0302 and DQB1*0201, found on the DR4 and DR3 haplotypes, respectively [7,8]. Although the DQB1 locus still represents the single most important indicator of susceptibility, DQA1*0501 and DQA1*0201 are both associated with type 1 diabetes [9].…”

Section: Introductionmentioning

confidence: 98%

HLA DR/DQ alleles and risk of type I diabetes in childhood: a population–based case–control study

et al. 2005

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The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta-parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97-8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77-12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11-0.57; OR=0.07, CI 0.02-0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97-190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36-549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.

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“…No reasonable further analyses can be based on this incomplete information. As a control we used background population frequencies of the class II haplotypes established in a previous study of the same populations (15).…”

Section: Methodsmentioning

confidence: 99%

Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations

Gombos¹,

Hermann²,

Kiviniemi³

et al. 2007

European Journal of Endocrinology

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Objective: Addison's disease is an organ-specific autoimmune disorder with a polygenic background. The aim of the study was to identify non-class II human leukocyte antigen (HLA) susceptibility genes for Addison's disease. Design and methods: Addison's disease patients from three European populations were analysed for selected HLA-DR-DQ alleles and for 11 microsatellite markers covering w4 Mb over the HLA region. Subjects were 69 patients with Addison's disease from Estonia (24), Finland (14) and Russia (31). Consecutively recruited healthy newborns from the same geographical regions were used as controls (269 Estonian, 1000 Finnish and 413 Russian). Association measures for HLA-DRB1, DQB1, DQA1 and 11 microsatellites between D6S273 and D6S2223 were taken. A low-resolution full-house typing was used for HLA class II genes, while microsatellite markers were studied using fluorescence-based DNA fragment sizing technology. Results: We confirmed that the HLA-DR3-DQ2 and the DQB1*0302-DRB1*0404 haplotypes confer disease susceptibility. In Russian patients, we also found an increase of DRB1*0403 allele, combined with DQB1*0305 allele in three out of six cases (P!0.0001). Analysis of 11 microsatellite markers including STR MICA confirmed the strong linkage in DR3-DQ2 haplotypes but DRB1*0404-DQB1*0302 haplotypes were diverse. MICA5.1 allele was found in 22 out of 24 Estonian patients, but results from Finnish and Russian patients did not support its independent role in disease susceptibility. Conclusion: HLA-DRB1*0403 was identified as a novel susceptibility allele for Addison's disease. Additionally, we found no evidence of a non-class II HLA disease susceptibility locus; however, the HLA-DR3-DQ2 haplotype appeared more conserved in patient groups with high DR-DQ2 frequencies.

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Distribution of insulin‐dependent diabetes mellitus (IDDM)‐related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region

Cited by 36 publications

References 12 publications

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?

HLA DR/DQ alleles and risk of type I diabetes in childhood: a population–based case–control study

Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations

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