Abstract
BackgroundGene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that C4 genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.MethodsA case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of C4 isotypes (C4A and C4B) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total C4, C4 isotypes (C4A and C4B) and C4 polymorphisms were estimated according to the occurrence of GD and its associated clinical features.ResultsIndividuals with 4, 2, and 2 copies of C4, C4A and C4B genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and p = 1.395 × 10-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total C4, C4 isotypes as well as C4 polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of C4A may associate with high risk toward vitiligo in patients with GD (p = 0.001, OR = 5.579, 95% CI: 1.659-18.763).ConclusionsThese results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.
Highlights
Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway
After adjusting for age, individuals with 4 copies of C4 gene were more susceptible to Graves’ disease (GD) (p = 0.001, odds ratio (OR) = 10.994, 95% confidence intervals (CI): 6.277-19.255) as compared to those without, whereas those with
For C4A gene, individuals with 2 copies of C4A increased the risk toward GD (p = 0.008, OR = 1.732, 95% CI: 1.190-2.520) whereas those with
Summary
Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that C4 genetic diversity may partially explain the development of Graves’ disease (GD) and the variation in its outcomes. Copy number variation (CNV) loci often contain genes engaged in host-environment interactions, including those involved in immune functions, which results in susceptibility or resistance to Complement component C4 (C4), located on chromosome 6q21.3, is encoded by 2 separate loci in the major histocompatibility complex class III region and derives 2 functionally distinct C4A and C4B isoforms [8]. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that C4 genetic diversity may partially explain the development of GD as well as the variation in its outcomes. We investigated the polymorphic variants of C4 that correlate with predisposition to this disease
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