Association study of the C3 gene with adult and childhood asthma

Abstract

Bronchial asthma (BA) is a multifactorial disorder, the development of which is affected by both environmental and genetic factors. The complement system plays an important role in immunological response against invading microorganisms. It has been shown that complement-C3-deficient mice have reduced inflammation of asthmatic airways. Previously, we reported the association of four single nuclear proteins (SNPs) in the exons of the C3 gene with childhood and adult BA. The C3 gene, however, is a large gene, and functional SNPs associated with susceptibility to BA have not yet been identified. We analyzed 26 SNPs in the C3 gene and its promoter region to narrow down the regions showing association with childhood and adult BA. Childhood and adult atopic BA patients and healthy child and adult controls were recruited from urban cities in Japan and genotyped. In SNP analysis, an SNP (SNP24, rs11569562) located in intron 31 of the C3 gene was associated with adult BA [corrected P (P cor ) = 0.030]. In linkage disequilibrium (LD) block 4 spanning exons 24-41, the frequency of the CCC haplotype in adult BA was significantly higher than that in adult controls (P cor = 0.038). Neither the SNP nor the haplotype showing association with adult BA demonstrated a significant association with serum total immunoglobulin E (IgE) level in BA patients and controls. Our results suggest that LD block 4 confers susceptibility to adult BA with mechanisms relevant to the effector phase of allergic inflammation.

Is Asthma Related to Choroidal Neovascularization?

“…Like CNV, BA is a multifunctional disorder with both environmental and genetic factors contributing to its development. Recent studies reveal that the complement system plays a crucial role in the development of immunological responses in BA by initiating and/or amplifying airway inflammation [16], [17]. Variations of genes in the complement system have been shown to confer susceptibility to BA, including complement factor 3(C3) and complement factor 4(C4).…”

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

“…Whereas the mechanism of this association remains uncertain, it should be noted that a similar genetic interval, incorporating intron 27, has also been associated with bronchial asthma, adding additional weight to our argument that non-coding variation in the central region of C3 is a true disease susceptibility effect. 17 It is important to compare our results with the only other study, in a Japanese population, to also report association between C3 polymorphisms and both serum C3 and SLE. 10 There are notable differences between the variants found to be associated with SLE.…”

Genes Associated with RSV Lower Respiratory Tract Infection and Asthma: The Application of Genetic Epidemiological Methods to Understand Causality

“…One study demonstrated significant associations with wheezing in the 15 months after RSV LRI ( IL19, IL20, MUC5AC, TNFRSF1B, C3, CTLA4, CXCL9, IL4R and IL7 ) [124], of which C3, CTLA4 and IL4R overlap with variants identified with asthma [125–129]. They also identified a functional SNP in IL13 associated with 6-year wheezing outcomes (n = 72) after RSV LRI [130], which has replicated inconsistently in studies of asthma [125].…”