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Clin Endocrinol (Oxf). 2009 Mar;70(3):358-62. doi: 10.1111/j.1365-2265.2008.03380.x. Epub 2008 Aug 15.

The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene predisposes to autoimmune Addison's disease.

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  • 1Institute of Human Genetics, Newcastle University, Newcastle Upon Tyne, UK.

Abstract

OBJECTIVE:

Previous studies of the association between autoimmune Addison's disease (AAD) and a nonsynonymous single nucleotide polymorphism (SNP) in the PTPN22 gene (C1858T, pR620W; SNP ID no. rs2476601) have shown conflicting results. We aimed to examine this association using additional cohorts of AAD subjects from the UK and Poland.

DESIGN:

DNA samples were obtained from UK and Polish AAD subjects (n = 251 and 87, respectively) and ethnically matched healthy controls (n = 429 and 236, respectively). Genotyping for the C1858T PTPN22 marker was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Meta-analysis of the results, together with those from three other populations, was performed using RevMan v5.0 software.

RESULTS:

In 251 UK AAD subjects the frequency of the PTPN22 1858T allele was 12.2% compared to 7.8% in healthy UK controls; P = 0.008. Similarly, in 87 Polish AAD subjects the PTPN22 1858T allele was found in 19.5% of alleles compared to 11.7% in healthy Polish subjects; P = 0.010. A meta-analysis, combining these result with published data for three other populations, involving 797 AAD subjects and 2032 controls in total, showed that the 1858T allele was associated with AAD susceptibility with a pooled odds ratio (OR) of 1.44 [95% confidence interval (CI) 1.21-1.72; P = 5.6 x 10(-5)], under a fixed-effects model.

CONCLUSION:

This study confirms the association between the PTPN22 1858T allele and AAD in an expanded UK cohort and in the previously unstudied Polish population. This meta-analysis allows for the first time a reliable estimate of the strength of effect of this autoimmune disease susceptibility allele across different European Caucasian populations.

PMID:
18710467
[PubMed - indexed for MEDLINE]
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