title: Association of the HLA-DRB1 with scleroderma in Chinese population.
abstract: Multiple alleles of the Human leukocyte antigen (HLA) DRB1 have been strongly associated with systemic sclerosis (SSc) and its clinical or serological subsets. However, the associations vary in different ethnic populations. To define SSc-risk and/or -protective alleles of HLA-DRB1 in Chinese population, we studied a Han Chinese cohort containing 585 patients with SSc and 458 gender-matched, unrelated controls. The HLA-DRB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher's test) from 2×2 tables of allele frequency and disease status. The major SSc-risk allele subtypes of HLA-DRB1 are the DRB1*15∶02 and *16∶02 in this Chinese cohort. Particularly, DRB1*15∶02 was most significantly associated with anti-centromere autoantibodies (ACA) positive, and DRB1*16∶02 with anti-topoisomerase I autoantibodies (ATA) positive patients. On the other hand, DRB1*01∶01 and *04∶06 were strong SSc-protective alleles in Chinese, especially in patients who were ACA positive and had diffuse cutaneous SSc (dcSSc), respectively. In addition, DRB1*11 and *07∶01 also showed significant association with SSc as a risk for and protection from SSc, respectively, and which is consistent with the studies of Spanish, US Caucasian and Hispanic populations. DRB1*15 was associated with ATA positive Chinese SSc that is consistent with Black South African and Korean SSc. These findings of HLA-DRB1 alleles in association with Chinese SSc provide the growing knowledge of genetics of SSc, and indicate that the genetic heterogeneity among ethnicities may significantly impact the complex trait of SSc.
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, the University of Texas Medical School at Houston, Houston, TX, United States of America; Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, Shanghai, China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: He
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China; Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Gansu College of Traditional Chinese Medicine, Lanzhou, Gansu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yi
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, the University of Texas Medical School at Houston, Houston, TX, United States of America.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Guo
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Shicheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Yiling Hospital, Shijiazhuang, Hebei Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Tu
authors.affiliation: Division of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Wu
authors.affiliation: Division of Rheumatology, Teaching Hospital of Chengdu University of TCM, Chengdu, Sichuan Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of pathology, Baylor College of Medicine, Michael E. DeBakey VA Medical Center, Houston, TX, United States of America.
authors.forename: Syeling
authors.initials: S
authors.lastname: Lai
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China; Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Zou
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, the University of Texas Medical School at Houston, Houston, TX, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, the University of Texas Medical School at Houston, Houston, TX, United States of America.
authors.forename: Shervin
authors.initials: S
authors.lastname: Assassi
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, the University of Texas Medical School at Houston, Houston, TX, United States of America.
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Mayes
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, the University of Texas Medical School at Houston, Houston, TX, United States of America.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
mesh_terms: D044466:Asian People / Q000208:ethnology; D002681:China / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D040641:Quantitative Trait Loci; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*
chemical_list: D059811:HLA-DRB1 Chains