OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.
OBJECTIVE:Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLEpatients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.
Authors: M Martins; A H Williams; M Comeau; M Marion; J T Ziegler; B I Freedman; J T Merrill; S B Glenn; J A Kelly; K M Sivils; J A James; J M Guthridge; M E Alarcón-Riquelme; S-C Bae; J-H Kim; D Kim; J-M Anaya; S A Boackle; L A Criswell; R P Kimberly; G S Alarcón; E E Brown; L M Vilá; M A Petri; R Ramsey-Goldman; T B Niewold; B P Tsao; G S Gilkeson; D L Kamen; C O Jacob; A M Stevens; P M Gaffney; J B Harley; C D Langefeld; C Fesel Journal: Genes Immun Date: 2015-01-08 Impact factor: 2.676
Authors: Patrick Coit; Matlock Jeffries; Nezam Altorok; Mikhail G Dozmorov; Kristi A Koelsch; Jonathan D Wren; Joan T Merrill; W Joseph McCune; Amr H Sawalha Journal: J Autoimmun Date: 2013-04-24 Impact factor: 7.094
Authors: Sharon A Chung; Elizabeth E Brown; Adrienne H Williams; Paula S Ramos; Celine C Berthier; Tushar Bhangale; Marta E Alarcon-Riquelme; Timothy W Behrens; Lindsey A Criswell; Deborah Cunninghame Graham; F Yesim Demirci; Jeffrey C Edberg; Patrick M Gaffney; John B Harley; Chaim O Jacob; M Ilyas Kamboh; Jennifer A Kelly; Susan Manzi; Kathy L Moser-Sivils; Laurie P Russell; Michelle Petri; Betty P Tsao; Tim J Vyse; Raphael Zidovetzki; Matthias Kretzler; Robert P Kimberly; Barry I Freedman; Robert R Graham; Carl D Langefeld Journal: J Am Soc Nephrol Date: 2014-06-12 Impact factor: 10.121
Authors: Angélica M Delgado-Vega; Manuel Martínez-Bueno; Nina Y Oparina; David López Herráez; Helga Kristjansdottir; Kristján Steinsson; Sergey V Kozyrev; Marta E Alarcón-Riquelme Journal: Sci Rep Date: 2018-06-08 Impact factor: 4.379
Authors: D L Morris; M M A Fernando; K E Taylor; S A Chung; J Nititham; M E Alarcón-Riquelme; L F Barcellos; T W Behrens; C Cotsapas; P M Gaffney; R R Graham; B A Pons-Estel; P K Gregersen; J B Harley; S L Hauser; G Hom; C D Langefeld; J A Noble; J D Rioux; M F Seldin; T J Vyse; L A Criswell Journal: Genes Immun Date: 2014-03-06 Impact factor: 2.676