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Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes.

ABSTRACT: Epidemiological data suggest a common genetic susceptibility to type 1 diabetes (T1D) and autoimmune thyroid disease (AITD).Our objective was to identify the joint susceptibility genes for T1D and AITD.We conducted a family-based linkage and association study.The study took place at an academic medical center.Participants included 55 multiplex families (290 individuals) in which T1D and AITD clustered (T1D-AITD families).We conducted tests for linkage and family-based associations (transmission disequilibrium test) with four candidate genes: human leukocyte antigen (HLA), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), insulin variable number of tandem repeats (VNTR), and thyroglobulin.Linkage evidence to HLA appeared when subjects with either T1D or AITD were considered affected [maximum LOD score (MLS), 2.2]. The major HLA haplotype contributing to the shared susceptibility was DR3-DQB1*0201, with DR3 conferring most of the shared risk. The CTLA-4 gene showed evidence for linkage only when individuals with both T1D and AITD were considered affected (MLS, 1.7), and the insulin VNTR showed evidence for linkage when individuals with either T1D or AITD were considered affected (MLS, 1.9); i.e. it may contribute to the familial aggregation of T1D and AITD.The HLA class II locus contributes to the shared risk for T1D and AITD, and the major HLA haplotype contributing to this association is DR3-DQB1*0201. Additional non-HLA loci contribute to the joint susceptibility to T1D and AITD, and two potential candidates include the CTLA-4 and insulin VNTR loci.

SUBMITTER: Golden B

PROVIDER: S-EPMC1317090 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature

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Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes.

Golden Brian B Levin Lara L Ban Yoshiyuki Y Concepcion Erlinda E Greenberg David A DA Tomer Yaron Y

The Journal of clinical endocrinology and metabolism 20050531 8

<h4>Context</h4>Epidemiological data suggest a common genetic susceptibility to type 1 diabetes (T1D) and autoimmune thyroid disease (AITD).<h4>Objective</h4>Our objective was to identify the joint susceptibility genes for T1D and AITD.<h4>Design</h4>We conducted a family-based linkage and association study.<h4>Setting</h4>The study took place at an academic medical center.<h4>Participants</h4>Participants included 55 multiplex families (290 individuals) in which T1D and AITD clustered (T1D-AITD ...[more]

PMID: 15928253

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Project description:BackgroundVitamin D is a hormone that is mainly produced in the skin upon ultraviolet B radiation exposure and has important influence on various organs. In recent years, data have been collected that vitamin D deficiency plays an important role in the development of various nonskeletal diseases, including autoimmune diseases. Chronic autoimmune thyroiditis (Hashimoto's thyroiditis) is one of the most common organ-specific autoimmune endocrine diseases. It is characterized by increased level of antithyroid peroxidase and/or antithyroglobulin antibodies in blood, which often leads to thyroid dysfunction and structural changes of the gland. There is an opinion that vitamin D deficiency may be considered as an important risk factor for development of chronic autoimmune thyroiditis, but data of various small studies are controversial. Despite the fact that Georgia is a sunny country, vitamin D deficiency is a widespread problem here. Thyroid diseases, including the chronic autoimmune thyroiditis, are also very common in Georgia. The aim of our research was to compare the level of vitamin D between the patients with chronic autoimmune thyroiditis and the healthy subjects.MethodsThis retrospective study enrolled subjects, who were 18-70 years old and visited the clinics "Cortex" and "National Institute of Endocrinology" in 2018 or in 2019 from mid-spring to mid-summer. Data of thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, antithyroglobulin antibodies, thyroid ultrasonography, and 25(OH) vitamin D were retrospectively analysed based on medical history. In total, data of 1295 patients were collected. The statistical processing of data was performed through the SPSS 20 program.ResultsThe negative association between thyroid-stimulating hormone, antithyroid peroxidase antibodies, antithyroglobulin antibodies, heterogeneous parenchyma of thyroid gland, and vitamin D was found in women. Statistically significant association was not detected in men.ConclusionsSerum vitamin D is lower in women with autoimmune thyroiditis and primary hypothyroidism. Further studies are needed to evaluate the influence of vitamin D supplementation on thyroid autoantibody positivity or primary hypothyroidism.

Project description:BackgroundRecent studies have reported associations between body mass index (BMI) and various autoimmune disorders. However, it is still uncertain whether there exists a direct cause-and-effect relationship between BMI and autoimmune thyroiditis (AIT). The aim of our study is to investigate the causal association between BMI and AIT.MethodsWe conducted a two-sample summary data Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary statistics data related to BMI as exposure, and GWAS summary statistic data sets for AIT as the outcome. Robustly associated single-nucleotide polymorphisms (SNPs) for BMI were selected as instrumental variables (IVs). We used the inverse variance weighted (IVW) method as the primary method and performed other MR methods such as MR-Egger regression, weighted median, simple mode, and weighted mode analyses for further validation. The slope of MR-Egger regression was used to correct for pleiotropy and provide estimates of causality. The p-value for the intercept in MR-Egger was utilized to detect any directional pleiotropic effects. Heterogeneity and sensitivity analyses were performed to assess the robustness of our findings.ResultsSeventy-eight SNPs were selected from GWAS on BMI as the IVs. Our MR analysis using the IVW method showed a potential causal association between BMI and AIT (OR = 3.071, 95% CI 1.324-7.118). Findings from other MR methods are non-significant, although the direction of effect is consistent. There was no evidence that the result was affected by genetic pleiotropy (MR-Egger regression intercept = 0.01, SE = 0.00025, p = 0.719). Heterogeneity and sensitivity analyses revealed no significant heterogeneity among SNPs, and no single SNP drove the observed associations.ConclusionOur findings suggest a potential causal association between BMI and AIT, which may provide a basis for further investigation into the relationship between BMI and AIT. Further studies are required as only the IVW method shows significant results, and the case sample size is small.

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Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes.

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Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes.

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