Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations
1
Issued Date
2024-03-08
Resource Type
eISSN
20538790
Scopus ID
2-s2.0-85187680649
Journal Title
Lupus Science and Medicine
Volume
11
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Lupus Science and Medicine Vol.11 No.1 (2024)
Suggested Citation
Tangtanatakul P., Lei Y., Jaiwan K., Yang W., Boonbangyang M., Kunhapan P., Sodsai P., Mahasirimongkol S., Pisitkun P., Yang Y., Eu-Ahsunthornwattana J., Aekplakorn W., Jinawath N., Neelapaichit N., Hirankarn N., Wang Y.F. Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations. Lupus Science and Medicine Vol.11 No.1 (2024). doi:10.1136/lupus-2023-001061 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/97711
Title
Association of genetic variation on X chromosome with systemic lupus erythematosus in both Thai and Chinese populations
Author's Affiliation
The Chinese University of Hong Kong, Shenzhen
Zhejiang University School of Medicine
Chulalongkorn University
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Thailand Ministry of Public Health
Mahidol University
The University of Hong Kong
Thailand National Science and Technology Development Agency
Faculty of Medicine, Chulalongkorn University
Zhejiang University School of Medicine
Chulalongkorn University
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Thailand Ministry of Public Health
Mahidol University
The University of Hong Kong
Thailand National Science and Technology Development Agency
Faculty of Medicine, Chulalongkorn University
Corresponding Author(s)
Other Contributor(s)
Abstract
Objectives X chromosome has been considered as a risk factor for SLE, which is a prototype of autoimmune diseases with a significant sex difference (female:male ratio is around 9:1). Our study aimed at exploring the association of genetic variants in X chromosome and investigating the influence of trisomy X in the development of SLE. Methods X chromosome-wide association studies were conducted using data from both Thai (835 patients with SLE and 2995 controls) and Chinese populations (1604 patients with SLE and 3324 controls). Association analyses were performed separately in females and males, followed by a meta-analysis of the sex-specific results. In addition, the dosage of X chromosome in females with SLE were also examined. Results Our analyses replicated the association of TMEM187-IRAK1-MECP2, TLR7, PRPS2 and GPR173 loci with SLE. We also identified two loci suggestively associated with SLE. In addition, making use of the difference in linkage disequilibrium between Thai and Chinese populations, a synonymous variant in TMEM187 was prioritised as a likely causal variant. This variant located in an active enhancer of immune-related cells, with the risk allele associated with decreased expression level of TMEM187. More importantly, we identified trisomy X (47,XXX) in 5 of 2231 (0.22%) females with SLE. The frequency is significantly higher than that found in the female controls (0.08%; two-sided exact binomial test P=0.002). Conclusion Our study confirmed previous SLE associations in X chromosome, and identified two loci suggestively associated with SLE. More importantly, our study indicated a higher risk of SLE for females with trisomy X.