title: CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians.
abstract: Limited data are available on the genetics of rheumatoid arthritis (RA) in Egyptians. Therefore, we investigated whether the confirmed genetic risk factors for RA in Europeans and/or Asians contribute to RA susceptibility in Egyptians.
  
  
  
  A set of seven single-nucleotide polymorphisms (SNPs) in the vicinity of CD28, TNFAIP3, PTPN22, PADI4 and HLA-DRA were tested in a large multi-centric RA cohort in Egypt, consisting of 394 cases and 398 matched controls. Patients were stratified based on the positivity of either anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor (RF).
  
  
  
  Significant association was evident for three SNPs in this cohort: the CD28 (rs1980422) variant showed a strong association in the whole cohort (P=0.000119) and in seropositive subsets of the disease (PACPA+=0.004; PRF+=0.0005). Upon stratification, the PTPN22 (rs2476601) and TNFAIP3(rs5029939) variants showed association only with ACPA positive (PACPA+=0.00573) and negative (PACPA-=0.00999) phenotypes, respectively.
  
  
  
  Our results suggest that CD28(rs1980422) and PTPN22(rs2476601) contribute to RA-susceptibility in Egyptians. Failure to replicate the association of PADI4(rs2240340)/(PADI4_94) in Egyptian RA patients provides further support for the notion that genetic architecture of RA is different in multiple populations of European, Asian, African, and Middle Eastern ancestries. Further investigation using large-scale studies is thus needed to maximize the power of genetic association.
authors.affiliation: Molecular Medicine Research Group, Department of Reproductive Medicine, Division of Medical Research, National Research Centre (NRC), 33 EL Bohouth St., Dokki, Giza P.O.12622, Egypt (Scopus affiliation ID 60014618); Department of Dermatology, University of Lübeck, Germany.
authors.forename: Mohsen M
authors.initials: MM
authors.lastname: Hegab
authors.affiliation: Molecular Medicine Research Group, Department of Reproductive Medicine, Division of Medical Research, National Research Centre (NRC), 33 EL Bohouth St., Dokki, Giza P.O.12622, Egypt (Scopus affiliation ID 60014618).
authors.forename: Aml Fawzy
authors.initials: AF
authors.lastname: Abdelwahab
authors.affiliation: Department of Rheumatology and Immunology, Benha Teaching Hospital, Egypt.
authors.forename: Ali M
authors.initials: AM
authors.lastname: El-Sayed Yousef
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Egypt.
authors.forename: Mohamed Nabil
authors.initials: MN
authors.lastname: Salem
authors.affiliation: Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Al-Azhar University, Egypt.
authors.forename: Walaa
authors.initials: W
authors.lastname: El-Baz
authors.affiliation: Department of Rheumatology and Immunology, Benha Teaching Hospital, Egypt.
authors.forename: Sherry
authors.initials: S
authors.lastname: Abdelrhman
authors.affiliation: Department of Rheumatology and Immunology, Benha Teaching Hospital, Egypt.
authors.forename: Fatemah
authors.initials: F
authors.lastname: Elshabacy
authors.affiliation: Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Ain Shams University, Egypt.
authors.forename: Abdelazim
authors.initials: A
authors.lastname: Alhefny
authors.affiliation: Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Al-Azhar University, Egypt.
authors.forename: Wagida
authors.initials: W
authors.lastname: Abouraya
authors.affiliation: Department of Dermatology, University of Lübeck, Germany.
authors.forename: Saleh Mohamed
authors.initials: SM
authors.lastname: Ibrahim
authors.affiliation: Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Cairo University, Egypt. Electronic address: gragab@kasralainy.edu.eg.
authors.forename: Gaafar
authors.initials: G
authors.lastname: Ragab
authors.forename: Janine Mia
authors.initials: JM
authors.lastname: Rudolph
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D018106:CD28 Antigens / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D055815:Young Adult
chemical_list: D018106:CD28 Antigens; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: ACPAs; Egyptians; RF; Rheumatoid arthritis; SNPs