Exome sequencing of Singapore Chinese anti-citrullinated-protein-antibody-positive rheumatoid arthritis patients.

Autor:	Leong KP; Khai Pang Leong, senior consultant, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital; Personalised Medicine Service, Tan Tock Seng Hospital, 11 Jalan Tock Seng, Singapore 308433., Yong MY; Mei Yun Yong, research manager, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tock Seng, Singapore 308433., Koh ET; Ee Tzun Koh, senior consultant, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tock Seng, Singapore 308433., Cheung PPM; Peter Pak Moon Cheung, senior consultant, Division of Rheumatology, National University Hospital, 5 Lower Kent Ridge Road; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597., Lahiri M; Manjari Lahiri, senior consultant, Division of Rheumatology, National University Hospital, 5 Lower Kent Ridge Road; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597., Ng CT; Chin Teck Ng, senior consultant, Department of Rheumatology and Immunology, Singapore General Hospital, Outram Road, Singapore 169608., Woo CM; Chia Mun Woo, research manager, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tock Seng, Singapore 308433., Goh LL; Liuh Ling Goh, laboratory director, Personalised Medicine Service, Tan Tock Seng Hospital, 11 Jalan Tock Seng, Singapore 308433., Lim SHH; Sandy Hong Hong Lim, research assistant, Division of Rheumatology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074., Dhanasekaran P; Preeti Dhanasekaran, research assistant, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597., Cheah GYM; Grace Yee May Cheah, research assistant, Department of Rheumatology and Immunology, Singapore General Hospital, Outram Road, Singapore 169608., Tan JWL; Justina Wei Lyn Tan, Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tock Seng, Singapore 308433., Hu W; Wenchao Hu, scientist, GRAT Pte Ltd., Chong ML; Mei Ling Chong, scientist, Department of Genetics, School of Medicine, Yale University, New Haven, CT, USA., Kumar V; Vikrant Kumar, research fellow, Duke-NUS Medical School, 8 College Rd, Singapore 169857., Davila S; Sonia Davila 8,9 , deputy director, Duke-NUS Medical School, 8 College Rd, Singapore 169857; SingHealth Duke-NUS Institute of Precision Medicine (PRISM), Singapore Health Services, 5 Hospital Drive, Singapore 169609.
Jazyk:	angličtina
Zdroj:	The Journal of rheumatology [J Rheumatol] 2024 Dec 01. Date of Electronic Publication: 2024 Dec 01.
DOI:	10.3899/jrheum.2024-0140
Abstrakt:	Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies (GWAS). To investigate the genetic predisposition of Chinese anti-cyclic-citrullinated-peptides-antibody-positive RA, we carried out an exome sequencing study. Methods: Patients were recruited from three major public hospitals in Singapore, Tan Tock Seng Hospital (TTSH), Singapore General Hospital and National University Health System. Controls came from an established exome collection and from the TTSH Health Control Biobank. All the participants were of Chinese descent. We performed whole-exome sequencing (WES) in 595 ACPA-positive RA patients and 1281 controls and validated the candidate variants by genotyping 795 RA cases and 600 controls. Results: The discovery cohort yielded 73 susceptibility SNVs that reached statistical significance. In the validation study with an independent cohort, two SNVs remained significant: PCNXL4 (p-value 1.50x10 -5 ) and DHRS7 (p-value 6.02x10 -5 ). The majority of known susceptibility foci are not captured by exome sequencing. Conclusion: In this WES study of ACPA-positive RA in Chinese patients, we discovered two new variants in PCNXL4 and DHRS7 associated with risk of the disease.
Databáze:	MEDLINE
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