CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians

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• 作者：Mohsen M. Hegab^a ; ^b ; Aml Fawzy Abdelwahab^a ; Ali M. El-Sayed Yousef^c ; Mohamed Nabil Salem^d ; Walaa El-Baz^e ; Sherry Abdelrhman^c ; Fatemah Elshabacy^c ; Abdelazim Alhefny^f ; Wagida Abouraya^e ; Saleh Mohamed Ibrahim^b ; Gaafar Ragab^g ; ^{gragab@kasralainy.edu.eg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACPA ; Anti-citrullinated protein antibodies ; CGA ; candidategene association ; CI ; confidence interval ; DAS-28 ; disease activity score ; ENSRA ; Egyptian network for the study of rheumatoid arthritis ; GWA ; genomewide association ; HLA ; the human leukocyte antigen ; HWE ; Hardy-Weinberg equilibrium ; MAF ; minor allele frequency ; MIM ; Mendelian inheritance in man ; OR ; odds ratio ; PADI4 ; peptidyl arginine deiminase type IV ; PTPN22 ; protein tyrosine phosphatase non-receptor type 22 ; RA ; rheumatoid arthritis
• 刊名：Human Immunology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：77
• 期：6
• 页码：522-526
• 全文大小：367 K

文摘

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 (P_ACPA+ = 0.004; P_RF+ = 0.0005). Upon stratification, the PTPN22 (rs2476601) and TNFAIP3(rs5029939) variants showed association only with ACPA positive (P_ACPA+ = 0.00573) and negative (P_ACPA− = 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.