title: Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.
abstract: Complement C3 and C4 play key roles in the main physiological activities of complement system, and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases. A two-stage genome-wide association study (GWAS) was performed for serum levels of C3 and C4. The first stage was conducted in 1,999 healthy Chinese men, and the second stage was performed in an additional 1,496 subjects. We identified two SNPs, rs3753394 in CFH gene and rs3745567 in C3 gene, that are significantly associated with serum C3 levels at a genome-wide significance level (P = 7.33 × 10(-11) and P = 1.83 × 10(-9), respectively). For C4, one large genomic region on chromosome 6p21.3 is significantly associated with serum C4 levels. Two SNPs (rs1052693 and rs11575839) were located in the MHC class I area that include HLA-A, HLA-C, and HLA-B genes. Two SNPs (rs2075799 and rs2857009) were located 5' and 3' of C4 gene. The other four SNPs, rs2071278, rs3763317, rs9276606, and rs241428, were located in the MHC class II region that includes HLA-DRA, HLA-DRB, and HLA-DQB genes. The combined P-values for those eight SNPs ranged from 3.19 × 10(-22) to 5.62 × 10(-97). HBsAg-positive subjects have significantly lower C3 and C4 protein concentrations compared with HBsAg-negative subjects (P<0.05). Our study is the first GWAS report which shows genetic components influence the levels of complement C3 and C4. Our significant findings provide novel insights of their related autoimmune, infectious diseases, and molecular mechanisms.
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Aihua
authors.initials: A
authors.lastname: Tan
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.forename: Junjie
authors.initials: J
authors.lastname: Feng
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lin
authors.forename: Zengfeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Minzhong
authors.initials: M
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Linjian
authors.initials: L
authors.lastname: Mo
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Liang
authors.forename: Deyi
authors.initials: D
authors.lastname: Shi
authors.forename: Zhang
authors.initials: Z
authors.lastname: Huang
authors.forename: Xianghua
authors.initials: X
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003176:Complement C3 / Q000235:genetics* / Q000378:metabolism; D003181:Complement C4 / Q000235:genetics* / Q000378:metabolism; D005802:Genes, MHC Class II; D055106:Genome-Wide Association Study; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059805:HLA-DR alpha-Chains / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044967:Serum / Q000378:metabolism*
chemical_list: D003176:Complement C3; D003181:Complement C4; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D059805:HLA-DR alpha-Chains; D006514:Hepatitis B Surface Antigens