{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:24:19Z","timestamp":1780471459612,"version":"3.54.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Gene copy number of complement component <jats:italic>C4<\/jats:italic>, 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 <jats:italic>C4<\/jats:italic> genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of <jats:italic>C4<\/jats:italic> isotypes (<jats:italic>C4A<\/jats:italic> and <jats:italic>C4B<\/jats:italic>) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total <jats:italic>C4, C4<\/jats:italic> isotypes (<jats:italic>C4A<\/jats:italic> and <jats:italic>C4B<\/jats:italic>) and <jats:italic>C4<\/jats:italic> polymorphisms were estimated according to the occurrence of GD and its associated clinical features.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Individuals with 4, 2, and 2 copies of <jats:italic>C4<\/jats:italic>, <jats:italic>C4A<\/jats:italic> and <jats:italic>C4B<\/jats:italic> 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 \u00d7 10-5, OR = 2.621, 95% CI: 1.791-3.835; and <jats:italic>p<\/jats:italic> = 1.395 \u00d7 10<jats:sup>-4<\/jats:sup>, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total <jats:italic>C4<\/jats:italic>, <jats:italic>C4<\/jats:italic> isotypes as well as <jats:italic>C4<\/jats:italic> polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, &lt;2 copies of <jats:italic>C4A<\/jats:italic> may associate with high risk toward vitiligo in patients with GD (<jats:italic>p<\/jats:italic> = 0.001, OR = 5.579, 95% CI: 1.659-18.763).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1423-0127-18-71","type":"journal-article","created":{"date-parts":[[2011,9,27]],"date-time":"2011-09-27T06:42:41Z","timestamp":1317105761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Association between copy number variation of complement component C4 and Graves' disease"],"prefix":"10.1186","volume":"18","author":[{"given":"Yu-Huei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chwen-Tzuei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ling","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhsin","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hai","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuu-Jen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,9,26]]},"reference":[{"issue":"2","key":"325_CR1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1046\/j.1365-2168.2001.01729-3.x","volume":"88","author":"A Mishra","year":"2001","unstructured":"Mishra A, Mishra SK: Multicentre study of thyroid nodules in patients with Graves' disease (Br J Surg 2000; 87: 1111-13). 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