{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:47:17Z","timestamp":1790624837990,"version":"4.1.0"},"reference-count":39,"publisher":"The Journal of Rheumatology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"accepted":{"date-parts":[[2012,10,19]]},"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is an essential cofactor in nitric oxide (NO) production. Polymorphisms in the<jats:italic>GCH1<\/jats:italic>gene have been implicated in protection against pain sensitivity. The aim of our study was to determine whether single-nucleotide polymorphisms (SNP) in the<jats:italic>GCH1<\/jats:italic>gene affect susceptibility and\/or pain sensitivity in fibromyalgia syndrome (FM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>A total of 409 patients with FM and 422 controls were enrolled. The alleles and genotypes at 4 positions [rs3783641(T&gt;A), rs841(C&gt;T), rs752688(C&gt;T), and rs4411417(T&gt;C)] in the<jats:italic>GCH1<\/jats:italic>gene were analyzed. The associations of the<jats:italic>GCH1<\/jats:italic>SNP with susceptibility and clinical measures in patients with FM were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>The frequencies of alleles and genotypes of the 4 SNP did not differ between patients with FM and healthy controls. Among 13 constructed haplotypes, we further examined 4 (CCTT, TTCT, TTCA, and CCTA) with &gt; 1% frequency in both FM and controls. No associations of<jats:italic>GCH1<\/jats:italic>polymorphisms with FM-related activity or severity indexes were found, although the number and total score of tender points in patients with FM differed among the 4 haplotypes (p = 0.03 and p = 0.01, respectively). The CCTA haplotype of<jats:italic>GCH1<\/jats:italic>was associated with significantly lower pain sensitivity and occurred less frequently than the CCTT haplotype in patients with FM (p = 0.04, OR 0.45, 95% CI 0.21\u20130.96).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>Our study provides evidence that certain<jats:italic>GCH1<\/jats:italic>haplotypes may be protective against susceptibility and pain sensitivity in FM. Our data suggest that NO is responsible for pain sensitivity in the pathogenesis of FM.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.120929","type":"journal-article","created":{"date-parts":[[2013,1,16]],"date-time":"2013-01-16T04:25:40Z","timestamp":1358310340000},"page":"316-322","source":"Crossref","is-referenced-by-count":34,"title":["Association of Guanosine Triphosphate Cyclohydrolase 1 Gene Polymorphisms with Fibromyalgia Syndrome in a Korean Population"],"prefix":"10.3899","volume":"40","author":[{"given":"SEONG-KYU","family":"KIM","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SEONG-HO","family":"KIM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SEONG-SU","family":"NAH","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JI HYUN","family":"LEE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SEUNG-JAE","family":"HONG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HYUN-SOOK","family":"KIM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HYE-SOON","family":"LEE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HYOUN AH","family":"KIM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHUNG-IL","family":"JOUNG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JISUK","family":"BAE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JUNG-YOON","family":"CHOE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SHIN-SEOK","family":"LEE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2013,1,15]]},"reference":[{"key":"2025021211251286000_40.3.316.1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3470001"},{"key":"2025021211251286000_40.3.316.2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1490"},{"key":"2025021211251286000_40.3.316.3","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-3-16"},{"key":"2025021211251286000_40.3.316.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2008.02.004"},{"key":"2025021211251286000_40.3.316.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.10.023"},{"key":"2025021211251286000_40.3.316.6","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-3-6"},{"key":"2025021211251286000_40.3.316.7","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-4-58"},{"key":"2025021211251286000_40.3.316.8","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-5-56"},{"key":"2025021211251286000_40.3.316.9","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199803000-00002"},{"key":"2025021211251286000_40.3.316.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2009.04.007"},{"key":"2025021211251286000_40.3.316.11","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-0896rev"},{"key":"2025021211251286000_40.3.316.12","first-page":"377","article-title":"Nitric oxide as a physiopathological factor in neuropsychiatric disorders","volume":"18","author":"Akyol","year":"2004","journal-title":"In Vivo"},{"key":"2025021211251286000_40.3.316.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00284-0"},{"key":"2025021211251286000_40.3.316.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-008-0738-x"},{"key":"2025021211251286000_40.3.316.15","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780330203"},{"key":"2025021211251286000_40.3.316.16","first-page":"377","article-title":"A standardized manual tender point survey. 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