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

Mohsen M. Hegab; Aml Fawzy Abdelwahab; Ali M. El-Sayed Yousef; Mohamed Nabil Salem; Walaa El-Baz; Sherry Abdelrhman; Fatemah Elshabacy; Abdelazim Alhefny; Wagida Abouraya; Saleh Mohamed Ibrahim; Gaafar Ragab

doi:10.1016/j.humimm.2016.04.018

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

Mohsen M. Hegab, Aml Fawzy Abdelwahab, Ali M. El-Sayed Yousef, Mohamed Nabil Salem, Walaa El-Baz, Sherry Abdelrhman, Fatemah Elshabacy, Abdelazim Alhefny, Wagida Abouraya, Saleh Mohamed Ibrahim, Gaafar Ragab^*

^*Corresponding author for this work

Clinic of Dermatology, Allergology and Venerology

17 Citations (Scopus)

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 (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.

Original language	English
Journal	Human Immunology
Volume	77
Issue number	6
Pages (from-to)	522-526
Number of pages	5
ISSN	0198-8859
DOIs	https://doi.org/10.1016/j.humimm.2016.04.018
Publication status	Published - 01.06.2016

Funding

The authors thank Dr. Wael El-Garf (deceased in May, 2014) for establishing and maintaining the Biobank at the NRC, Ms. Julia Bischoff for her contribution in the statistical analysis and Prof. Dr. Laila Hegazy for support in Biobanking. The authors would like to thank the ENSRA members: Prof. Dr. Manal El-Meniawy, Prof. Dr. Hala El-Guindy, Dr. Mary Wadie, Dr. Amal Fouad, Dr. Heba Mahmoud, Dr. Mohammed Ahmed, Dr. Rasmia Elgohary, Dr. Zeinab Al-Nahas and Dr. Hala Ramadan for assistance in patient recruitment. The authors would like to thank Mr. Ahmed Farouk Yousef for developing the electronic database. The authors would also like to thank Dr. Amr Fayez and Dr. Shaaban Elsayed for providing controls. The authors would also like to thank Mr. Mohamed Maghawry, Mr. Hazem Hamza, and Mohamed Reda for their assistance. The study was supported by grants from the German Science Foundation (DFG, Germany; ExC306/1) and BMBF (IMPAM) to S.I. as well as domestic funding from the NRC of Egypt to M.M.H.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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@article{233291f843fd4e1883974619aa2f4662,

title = "CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians",

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.",

author = "Hegab, \{Mohsen M.\} and Abdelwahab, \{Aml Fawzy\} and \{El-Sayed Yousef\}, \{Ali M.\} and Salem, \{Mohamed Nabil\} and Walaa El-Baz and Sherry Abdelrhman and Fatemah Elshabacy and Abdelazim Alhefny and Wagida Abouraya and Ibrahim, \{Saleh Mohamed\} and Gaafar Ragab",

year = "2016",

month = jun,

day = "1",

doi = "10.1016/j.humimm.2016.04.018",

language = "English",

volume = "77",

pages = "522--526",

journal = "Human Immunology",

issn = "0198-8859",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - CD28 and PTPN22 are associated with susceptibility to rheumatoid arthritis in Egyptians

AU - Hegab, Mohsen M.

AU - Abdelwahab, Aml Fawzy

AU - El-Sayed Yousef, Ali M.

AU - Salem, Mohamed Nabil

AU - El-Baz, Walaa

AU - Abdelrhman, Sherry

AU - Elshabacy, Fatemah

AU - Alhefny, Abdelazim

AU - Abouraya, Wagida

AU - Ibrahim, Saleh Mohamed

AU - Ragab, Gaafar

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84975105639

U2 - 10.1016/j.humimm.2016.04.018

DO - 10.1016/j.humimm.2016.04.018

M3 - Journal articles

C2 - 27125674

AN - SCOPUS:84975105639

SN - 0198-8859

VL - 77

SP - 522

EP - 526

JO - Human Immunology

JF - Human Immunology

IS - 6

ER -

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

Abstract

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