TY - JOUR
T1 - Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects
AU - Yang, Xiaobo
AU - Sun, Jielin
AU - Gao, Yong
AU - Tan, Aihua
AU - Zhang, Haiying
AU - Hu, Yanling
AU - Feng, Junjie
AU - Qin, Xue
AU - Tao, Sha
AU - Chen, Zhuo
AU - Kim, Seong Tae
AU - Peng, Tao
AU - Liao, Ming
AU - Lin, Xiaoling
AU - Zhang, Zengfeng
AU - Tang, Minzhong
AU - Li, Li
AU - Mo, Linjian
AU - Liang, Zhengjia
AU - Shi, Deyi
AU - Huang, Zhang
AU - Huang, Xianghua
AU - Liu, Ming
AU - Liu, Qian
AU - Zhang, Shijun
AU - Trent, Jeffrey M.
AU - Zheng, S. Lilly
AU - Xu, Jianfeng
AU - Mo, Zengnan
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pgen.1002916
DO - 10.1371/journal.pgen.1002916
M3 - Article
C2 - 23028341
AN - SCOPUS:84866928184
SN - 1553-7390
VL - 8
JO - PLoS genetics
JF - PLoS genetics
IS - 9
M1 - e1002916
ER -