Haplotypes of GTP Cyclophydrolase Gene Polymorphisms Are Protective in the Susceptibility of Fibromyalgia Syndrome

Hwajeong Lee¹, Shin-Seok Lee², Seong-Kyu Kim³, Jung-Yoon Choe⁴, Seong-Ho Kim KIM⁵, Seong-Su Nah⁶, Ji Hyun Lee⁷, Seung-Jae Hong⁸, Hyun-Sook Kim⁹, Hye-Soon Lee¹⁰, Hyun Ah Kim¹¹ and Chung-Il Joung¹², ¹Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea, ²Dept of Int Med/Rheumatology, Chonnam National University Medical School, Gwangju, South Korea, ³Catholic University of Daegu School of Medicine, Daegu, South Korea, ⁴Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea, ⁵Department of Internal Medicine,, Inje University Haeundae Paik Hospital, Busan, South Korea, ⁶Department of Internal Medicine, Soonchunhyang University, College of Medicine, Cheonan, South Korea, ⁷Division of Rheumatology, Department of Internal Medicine, Maryknoll Medical Center, Busan, South Korea, ⁸Division of Rheumatology, Department of Internal Medicine, Kyung Hee University, Seoul, South Korea, ⁹Internal Medicine, Chosun University Hospital, Gwangju, South Korea, ¹⁰Department of Rheumatology, Hanyang University Guri Hospital, Guri, South Korea, ¹¹Division of Rheumatology, Department of Internal Medicine, Hallym university, Kyunggi, South Korea, ¹²Department of Internal Medicine, Konyang university hospital, Daejeon, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: fibromyalgia, pain and polymorphism

Session Information

Title: Fibromyalgia and Soft Tissue Disorders

Session Type: Abstract Submissions (ACR)

Background/Purpose: Guanosine triphosphate cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, which is an essential co-factor in nitric oxide (NO) production. Polymorphisms in the GCH1 gene have been implicated in protection against pain sensitivity. Our study was to determine whether single nucleotide polymorphisms (SNPs) in the GCH1 gene affect susceptibility and/or pain sensitivity in fibromyalgia syndrome (FMS).

Methods: A total of 409 FMS patients and 422 controls were enrolled. The alleles and genotypes at four positions, rs3783641(T>A), rs841(C>T), rs752688(C>T), and rs4411417(T>C), in the GCH1 gene were analyzed. The associations of the GCH1 SNPs with susceptibility and clinical parameters in FMS patients were assessed.

Results: The frequencies of alleles and genotypes of the four SNPs did not differ between FMS patients and healthy controls. Among 13 constructed haplotypes, we further examined four (CCTT, TTCT, TTCA, and CCTA) with >1% frequency in both FMS and controls. No associations of GCH1 polymorphisms with FMS-related activity or severity indexes were found, although the number and total score of tender points in FMS patients differed among the four haplotypes (p = 0.03 and p = 0.01, respectively). The CCTA haplotype of GCH1 was associated with significantly lower pain sensitivity and occurred less frequently than the CCTT haplotype in FMS patients (OR = 0.45; 95% CI, 0.21–0.96).

Conclusion: This study provides evidence that certain GCH1 haplotypes may be protective against susceptibility and pain sensitivity in FMS. Our data also suggest that NO is responsible for pain sensitivity in the pathogenesis of FMS.

Disclosure:

H. Lee,
None;

S. S. Lee,
None;

S. K. Kim,
None;

J. Y. Choe,
None;

S. H. K. KIM,
None;

S. S. Nah,
None;

J. H. Lee,
None;

S. J. Hong,
None;

H. S. Kim,
None;

H. S. Lee,
None;

H. A. Kim,
None;

C. I. Joung,
None.

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/haplotypes-of-gtp-cyclophydrolase-gene-polymorphisms-are-protective-in-the-susceptibility-of-fibromyalgia-syndrome/