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


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.


CONCLUSIONS
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.
Kahles
Heinrich
H
Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Ramos-Lopez
Elizabeth
E
Lange
Britta
B
Zwermann
Oliver
O
Reincke
Martin
M
Badenhoop
Klaus
K
D000224:Addison Disease / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005858:Germany; D050031:Hashimoto Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012737:Sex Factors
C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases