A promoter polymorphism of the CYP27B1 gene is associated with Addison's disease, Hashimoto's thyroiditis, Graves' disease and type 1 diabetes mellitus in Germans

BACKGROUND: CYP27B1 hydroxylase catalyzes the conversion of 25 hydroxyvitamin D(3) (25OHD(3)) to 1,25(OH)(2)D(3), the most active natural vitamin D metabolite, which plays a role in the regulation of immunity and cell proliferation. We therefore investigated two single nucleotide polymorphisms in the CYP27B1 hydroxylase gene for an association with Addison's disease, Hashimoto's thyroiditis, Graves' disease and type 1 diabetes mellitus. METHODS: Patients with Addison's disease (n=124), Hashimoto's thyroiditis (n=139), Graves' disease (n=334), type 1 diabetes mellitus (n=252) and healthy controls (n=320) were genotyped for the promoter (-1260) C/A polymorphism and for the intron 6 (+2838) C/T polymorphism of the CYP27B1 gene. Patients and controls were compared using genotype-wise and allele-wise X(2) testing. RESULTS: A significant association was found between allelic variation of the promoter (-1260) C/A polymorphism and Addison's disease, Hashimoto's thyroiditis, Graves' disease and type 1 diabetes mellitus (P=0.0062, P=0.0173, P=0.0094 and P=0.0028 respectively). Significant differences were also observed for the intron 6 (+2838) C/T polymorphism (P=0.0058) in Hashimoto's thyroiditis but not for the other autoimmune endocrine diseases. CONCLUSIONS: The CYP27B1 promoter (-1260) C/A polymorphism appears to be associated with endocrine autoimmune diseases but the CYP27B1 intron 6 (+2838) C/T polymorphism appears to be associated only with Hashimoto's thyroiditis. These results imply a regulatory difference of the CYP27B1 hydroxylase to predispose to endocrine autoimmunity.

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Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto’s thyroiditis or Addison’s disease in the German population

Acta Endocrinologica ◽

10.1530/eje.1.02035 ◽

2005 ◽

Vol 153 (6) ◽

pp. 895-899 ◽

Cited By ~ 74

Author(s):

Heinrich Kahles ◽

Elizabeth Ramos-Lopez ◽

Britta Lange ◽

Oliver Zwermann ◽

Martin Reincke ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Hashimoto’S Thyroiditis ◽

Addison’S Disease ◽

Hashimoto's Thyroiditis ◽

Addison's Disease ◽

Healthy Controls ◽

Significant Difference

Background: Endocrine autoimmune disorders share genetic susceptibility loci, causing a disordered T-cell activation and homeostasis (HLA class II genes, CTLA-4). Recent studies showed a genetic variation within the PTPN22 gene to be an additional risk factor. Materials and Methods: Patients with type 1 diabetes (n = 220), Hashimoto’s thyroiditis (n = 94), Addison’s disease (n = 121) and healthy controls (n = 239) were genotyped for the gene polymorphism PTPN22 1858 C/T. Results: Our study confirms a significant association between allelic variation of the PTPN22 1858 C/T polymorphism and type 1 diabetes mellitus (T1D). 1858T was observed more frequently in T1D patients (19.3% vs 11.3%, P = 0.0009; odds ratio for allele T = 1.88, 95% confidence interval [1.3–2.7]). Furthermore, we found a strong association in female patients with T1D (P = 0.0003), whereas there was no significant difference between male patients with type 1 diabetes and male controls. No significant difference was observed between the distribution of PTPN22 C/T in patients with Hashimoto’s thyroiditis or Addison’s disease and healthy controls. Conclusion: The PTPN22 polymorphism 1858 C/T may be involved in the pathogenesis of type 1 diabetes mellitus by a sex-specific mechanism that contributes to susceptibility in females.

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The CTLA4 region as a general autoimmunity factor: An extended pedigree provides evidence for synergy with the HLA locus in the etiology of type 1 diabetes mellitus, Hashimoto's thyroiditis and Graves' disease

European Journal of Human Genetics ◽

10.1038/sj.ejhg.5200903 ◽

2003 ◽

Vol 11 (1) ◽

pp. 81-84 ◽

Cited By ~ 35

Author(s):

Elisabet Einarsdottir ◽

Ingegerd Söderström ◽

Anna Löfgren-Burström ◽

Susann Haraldsson ◽

Sofie Nilsson-Ardnor ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Hashimoto’S Thyroiditis ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Extended Pedigree

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Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome

Clinical Endocrinology ◽

10.1046/j.1365-2265.2001.01230.x ◽

2001 ◽

Vol 54 (3) ◽

pp. 335-338 ◽

Cited By ~ 42

Author(s):

G. Meyer ◽

H. Donner ◽

J. Herwig ◽

H. Böhles ◽

K. H. Usadel ◽

...

Keyword(s):

Type 1 Diabetes ◽

Hashimoto’S Thyroiditis ◽

Addison’S Disease ◽

Disease Type ◽

Hashimoto's Thyroiditis ◽

Addison's Disease ◽

Graves Disease

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Strategies for Insulin Delivery in a Patient With Type 2 Autoimmune Polyglandular Syndrome (APS-2): Type 1 Diabetes Mellitus, Addison's Disease, and Hashimoto's Thyroiditis

Journal of Pediatric Nursing ◽

10.1016/j.pedn.2011.04.009 ◽

2011 ◽

Vol 26 (3) ◽

pp. 276

Author(s):

Toni Davis

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Addison’S Disease ◽

Insulin Delivery ◽

Hashimoto's Thyroiditis ◽

Addison's Disease ◽

Autoimmune Polyglandular Syndrome

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Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves' disease, Hashimoto's thyroiditis and type 1 diabetes mellitus

Acta Endocrinologica ◽

10.1530/eje.0.1460777 ◽

2002 ◽

pp. 777-781 ◽

Cited By ~ 27

Author(s):

MA Pani ◽

K Regulla ◽

M Segni ◽

M Krause ◽

S Hofmann ◽

...

Keyword(s):

Diabetes Mellitus ◽

Vitamin D ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Hashimoto’S Thyroiditis ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Hla Dq ◽

Hla Dq2

OBJECTIVE: The vitamin D endocrine system plays a role in the regulation of (auto)immunity and cell proliferation. Vitamin D 1alpha-hydroxylase (CYP1alpha) is one of the key enzymes regulating both systemic and tissue levels of 1,25-dihyroxyvitamin D(3) (1,25(OH)(2)D(3)). Administration of 1,25(OH)(2)D(3), whose serum levels were found to be reduced in type 1 diabetes and thyroid autoimmunity, prevents these diseases in animal models. We therefore investigated a recently reported CYP1alpha polymorphism for an association with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. DESIGN AND METHODS: Four hundred and seven Caucasian pedigrees with one offspring affected by either type 1 diabetes (209 families), Graves' disease (92 families) or Hashimoto's thyroiditis (106 families) were genotyped for a C/T polymorphism in intron 6 of the CYP1alpha gene on chromosome 12q13.1-13.3 and transmission disequilibrium testing (TDT) was performed. Subsets of affected offspring stratified for HLA-DQ haplotype were compared using chi(2) testing. RESULTS: There was no deviation from the expected transmission frequency in either type 1 diabetes mellitus (P=0.825), Graves' disease (P=0.909) or Hashimoto's thyroiditis (P=0.204). However, in Hashimoto's thyroiditis the CYP1alpha C allele was significantly more often transmitted to HLA-DQ2(-) patients (27 transmitted vs 14 not transmitted; TDT: P=0.042) than expected. The C allele was less often transmitted to HLA-DQ2(+) patients (9 transmitted vs 12 not transmitted; TDT: P=0.513), although the difference was not significant (chi(2) test: P=0.143). A similar difference was observed in type 1 diabetes between offspring with high and low risk HLA-DQ haplotypes (chi(2) test: P=0.095). CONCLUSIONS: The CYP1alpha intron 6 polymorphism appears not to be associated with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. A potential association in subsets of patients with type 1 diabetes and Hashimoto's thyroiditis should be further investigated as well as its functional implications.

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