Abstract for presentation at 11th International Congress of Human Genetics

Genetic Association of the PTPN22 R620W Polymorphism in Familial and Sporadic SLE in European-Americans

  • Kenneth Kaufman, Oklahoma Medical Research Foundation; US Veterans Affairs Medical Center, OK, United States
  • Jennifer Kelly, Oklahoma Medical Research Foundation, OK, United States
  • Billy Herring, Oklahoma Medical Research Foundation, OK, United States
  • Bahram Namjou, Oklahoma Medical Research Foundation, OK, United States
  • Summer Frank, Oklahoma Medical Research Foundation, OK, United States
  • Gail Bruner, Oklahoma Medical Research Foundation, OK, United States
  • Judith James, Oklahoma Medical Research Foundation; University of Oklahoma, OK, United States
  • John Harley, Oklahoma Medical Research Foundation; US Veterans Affairs Medical Center; University of Oklahoma, OK, United States

    • Purpose: The R620W (1858C→T, rs2476601) polymorphism in the PTPN22 gene has been implicated in type 1 diabetes, rheumatoid arthritis, Graves’ disease, Hashimoto’s thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). This study evaluates this polymorphism in familial and sporadic SLE.
    Methods: A total of 4982 samples were genotyped (1680 SLE cases, 1834 family members and 1467 controls). Both population-based case-control and family-based association designs were employed.
    Results: In the European-American (EA) familial SLE cohort, the minor 1858T allele was more common in randomly selected cases compared to controls (χ2=5.89, p=0.015, OR=1.47 (95% CI: 1.08-2.00)). The heterozygous 1858C/T genotype was also associated with these EA cases compared to controls (OR=1.64 (95% CI: 1.16-2.32)). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (χ2 =5.951, p=0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the EA sporadic SLE cases compared to controls nor did they have preferential transmission of the 1858T. Indeed, the difference of the 1858T allele frequency between the EA familial and sporadic cases was measurable (allelic χ2=4.02, p=0.04, OR=1.49 (95% CI: 1.01-2.20)). In the meantime, our data also show that among SLE cases 1858T is separately associated with type 1 diabetes and with autoimmune thyroid disease, confirming the findings of others.
    Conclusion: In summary, the 1858T allele of PTPN22 is associated with EA familial SLE, but not EA sporadic SLE, thereby potentiall explaining previously contradictory reports.

    Conference Organiser - ICMS Pty Ltd