Iranian Journal of Psychiatry 2017. 12(3):219-222.

Report a Novel Mutation in Human Prostacyclin Receptor Gene in patient affected with Migraine
Majid Kheirollahi, Mohammad Reza Pourreza, Fariborz Khorvash, Mohammad Kazemi, Gilda Amini


Objective: The human prostacyclin receptor gene (PTGIR) encodes the human prostacyclin (PGI2) receptor. PTGIR is a part of vasodilator system during the migraine attacks and probably has an important role in the mechanism of this disease. Materials and Methods: We used direct PCR and sequencing to determine the any variants in PTGIR gene. A blood sample was collected from the patients and genomic DNA was extracted. Polymerase chain reaction was carried out on extracted DNA. The PCR products were then sequenced using a cycle sequencing kit, on an automated DNA sequencing machine. Results: In reviewing of familial and clinopathological of these two patients, both patients have migraines with visual aura and their mothers also are suffering from migraines. Their parents had been married strangers. Direct sequencing analysis of exon 2 of the PTGIR gene showing the presence of two mutations in two patients. These mutations were heterozygote that made the following changes; g.1626T>A, c.754T>A, cDNA.867T>A, and p.S252T for the first mutation and c.753C>T, cDNA866C>T, g.1625C>T, p.C251C for the second mutation. The first mutation alters the amino acid and is a novel mutation. The second change is a conservative mutation that have already been reported. Conclusion: The prediction results predicted the variant would negatively affect the protein’s function and seems to be disease causing. Although functional analysis is required to confirm the association between the variant and the disease.


Migraine ; Mutation; Prostacyclin Receptor Gene

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Piane M, Lulli P, Farinelli I, Simeoni S, De Filippis S, Patacchioli FR, et al. Genetics of migraine and pharmacogenomics: some considerations. J Headache Pain. 2007 Dec;8(6):334-9.

Bartleson JD, Cutrer FM. Migraine update. Diagnosis and treatment. Minn Med. 2010 May;93(5):36-41.

Goadsby PJ. The vascular theory of migraine—a great story wrecked by the facts. Brain. 2009;132(1):6-7.

Brennan KC, Charles A. An update on the blood vessel in migraine. Current Opinion in Neurology. 2010;23(3):266–74.

Dodick DW. Examining the essence of migraine--is it the blood vessel or the brain? A debate. Headache. 2008 Apr;48(4):661-7.

Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999;79:1193–226.

Ogawa Y. Structural organization and chromosomal assignment of the human prostacyclin receptor gene. Genomics. 1995;27(1):142–8.

Giguere V, Gallant MA, de Brum-Fernandes AJ, Parent JL. Role of extracellular cysteine residues in dimerization/oligomerization of the human prostacyclin receptor. Eur J Pharmacol. 2004;494:11-22.

Stitham J, Gleim SR, Douville K, Arehart E, Hwa J. Versatility and differential roles of cysteine residues in human prostacyclin receptor structure and function. J Biol Chem. 2006;281:37227–36.

Martin KA, Gleim S, Elderon L, Fetalvero K, Hwa J. The human prostacyclin receptor from structure function to disease. Prog Mol Biol Transl Sci. 2009;89:133–66.

Stitham J, Stojanovic A, Hwa J. Impaired receptor binding and activation associated with a human prostacyclin receptor polymorphism. J Biol Chem. 2002;277:15439–44.

Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, et al. Catalog of 178 variations in the Japanese population among eight human genes encoding G protein-coupled receptors (GPCRs). J Hum Genet. 2003;48:461–8.

Stitham J, Arehart EJ, Gleim S, Douville KL, MacKenzie T, Hwa J. Arginine (CGC) codon targeting in the human prostacyclin receptor gene (PTGIR) and G-protein coupled receptors (GPCR). Gene. 2007;396(1):180–7.

Stitham J, Arehart E, Gleim SR, Li N, Douville K, Hwa J. New insights into human prostacyclin receptor structure and function through natural and synthetic mutations of transmembrane charged residues. Br J Pharmacol. 2007;152:513–22.

Arehart E, Stitham J, Asselbergs FW, Douville K, MacKenzie T, Fetalvero KM, et al. Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circ Res. 2008;102(8):986-93.

Stitham J, Arehart E, Elderon L, Gleim SR, Douville K, Kasza Z, et al. Comprehensive biochemical analysis of rare prostacyclin receptor variants: study of association of signaling with coronary artery obstruction. J Biol Chem. 2011;4(9):7060-9.


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