The heritability and genetics of complement C3 expression in UK SLE families

Rhodes, B; Hunnangkul, S; Morris, DL; Hsaio, LC; Graham, DSC; Nitsch, D; Whittaker, JC; Vyse, TJ; (2009) The heritability and genetics of complement C3 expression in UK SLE families. Genes and immunity, 10 (5). pp. 525-530. ISSN 1466-4879 DOI:

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As the central component of the complement system, C3 has sensory and effector functions bridging innate and adaptive immunity. It is plausible that common genetic variation at C3 determines either serum C3 level or susceptibility to systemic lupus erythematosus (SLE), but only a single, Japanese, study has currently showed genetic association. In a cohort of 1371 individuals from 393 UK white European SLE families, we quantified serum C3 and genotyped C3 tagSNPs. Using a Bayesian variance components model, we estimated 39.6% serum C3 heritability. Genotype/serum C3 association was determined by mixed linear models. Single nucleotide polymorphism (SNP) rs344555, located in a haplotype block incorporating the 3 0 end of C3, was associated with serum C3 (P = 0.007), with weaker associations observed for other SNPs in this block. In an extended cohort of 585 SLE families the association between C3 variants and SLE was assessed by transmission disequilibrium test. SNP rs3745568 was associated with SLE (P = 0.0046), but not with serum C3. Our disease associated SNP differs from that highlighted in the Japanese study; however, we replicate their finding that genetic variants at the 30 end of C3 are associated with serum C3. Larger studies and further fine mapping will be required to definitively identify functional variants. Genes and Immunity (2009) 10, 525-530; doi: 10.1038/gene.2009.23; published online 23 April 2009

Item Type: Article
Keywords: Complement C3, genetics, European Continental Ancestry Group, genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Great Britain, Humans, Lupus Erythematosus, Systemic, genetics, immunology, Male, Middle Aged, Polymorphism, Single Nucleotide
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 19387462
Web of Science ID: 268168800019


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