Association between copy number variation of complement component C4 and Graves' disease

作者：Liu Yu Huei; Wan Lei; Chang Chwen Tzuei; Liao Wen Ling; Chen Wen Chi; Tsai Yuhsin; Tsai Chang Hai; Tsai Fuu Jen^*

来源：Journal of Biomedical Science, 2011, 18: 71.

DOI：10.1186/1423-0127-18-71

Background: 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.
Methods: A 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.
Results: Individuals 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 x 10-5, OR = 2.621, 95% CI: 1.791-3.835; and p = 1.395 x 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).
Conclusions: These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.

• 出版日期2011-9-26
• 单位中国医科大学