Mohsen M Hegab1, Aml Fawzy Abdelwahab2, Ali M El-Sayed Yousef3, Mohamed Nabil Salem4, Walaa El-Baz5, Sherry Abdelrhman3, Fatemah Elshabacy3, Abdelazim Alhefny6, Wagida Abouraya5, Saleh Mohamed Ibrahim7, Gaafar Ragab8, Janine Mia Rudolph. 1. 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. 2. 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). 3. Department of Rheumatology and Immunology, Benha Teaching Hospital, Egypt. 4. Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Egypt. 5. Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Al-Azhar University, Egypt. 6. Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Ain Shams University, Egypt. 7. Department of Dermatology, University of Lübeck, Germany. 8. Department of Internal Medicine, Rheumatology & Immunology Unit, Faculty of Medicine, Cairo University, Egypt. Electronic address: gragab@kasralainy.edu.eg.
Abstract
OBJECTIVE: 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. SUBJECTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. SUBJECTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.