title: PTPN22 1858T is not a risk factor for North American pemphigus vulgaris.
abstract: Alterations in the protein tyrosine phosphatase N22 (PTPN22) gene affect the threshold for lymphocyte activation. The PTPN22 1858T polymorphism leads to uninhibited T-cell receptor cascade propagation. An elevated PTPN22 1858C/T genotype frequency has been correlated with several autoimmune disorders which have T-cell and humoral components. However, a recent Tunisian report demonstrated no association between PTPN22 1858T and patients with Pemphigus vulgaris (PV), an autoantibody-associated blistering disorder. Because PTPN22 1858T allele frequency is known to vary across ethnic populations, we conducted a case-control study investigating the relationship between PTPN22 1858T and PV in North American patients of either Ashkenazi Jewish or Caucasian (non-Ashkenazi) decent. Participant genotype was determined in 102 PV patients and 102 healthy controls by restriction fragment length polymorphism-polymerase chain reaction genotyping. Relationships were calculated using Fisher's exact tests and chi-squared tests. We report that the PTPN22 1858C/T genotype is not significantly associated with PV in either Caucasians (P = 0.83) or Ashkenazi Jews (P = 0.60). Further stratification of the patient population by gender, age of disease onset, HLA-type, family history of autoimmune disease, history of anti-desmoglein (anti-Dsg) 3 or anti-Dsg1 antibody response, history of lesion morphology, and disease duration did not uncover significant associations between the PTPN22 1858T allele and PV subgroups. Our data indicate that the PTPN22 1858T mutation is not associated with PV in the North American population. We do observe an elevation of PTPN22 1858C/T genotype frequency in male PV patients. Further investigation will be required to determine if this trend reaches significance in larger studies.
authors.affiliation: Division of Dermatology and Cutaneous Sciences, Center for Investigative Dermatology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Sachdev
authors.forename: Dhaval G
authors.initials: DG
authors.lastname: Bhanusali
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Patterson
authors.forename: Matt B
authors.initials: MB
authors.lastname: Zamora
authors.forename: Apram
authors.initials: A
authors.lastname: Ghuman
authors.forename: John A
authors.initials: JA
authors.lastname: Gerlach
authors.forename: Animesh A
authors.initials: AA
authors.lastname: Sinha
mesh_terms: D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D051183:Desmoglein 1 / Q000276:immunology; D051184:Desmoglein 3 / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009656:North America; D010392:Pemphigus / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D001323:Autoantibodies; D017931:DNA Primers; C495297:DSG1 protein, human; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22