G protein beta3 polymorphism and triptan response in cluster headache.

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Schurks M, Kurth T, Stude P, Rimmbach C, de Jesus J, Jonjic M, Diener HC, Rosskopf D

G protein beta3 polymorphism and triptan response in cluster headache.

Clin Pharmacol Ther. 2007 Oct;82(4):396-401. Epub 2007 Mar 14.

PubMed ID

17361120 [ View in PubMed

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Abstract

Only about 70% of migraine and cluster headache (CH) patients report significant treatment responses to triptans, which are agonists at 5-HT(1B/D) receptors belonging to the family of G protein-coupled receptors. We analyzed whether a common polymorphism in the gene for the G protein beta3 subunit (GNB3 C825T) modulates responder rates to triptans among a cohort of 231 unrelated Caucasian CH patients. A total of 180 CH patients used triptans, of whom 71.1% reported treatment success. The adjusted odds ratio for treatment response to triptans for heterozygous carriers of the GNB3 825T allele was 2.96 (95% confidence interval 1.34-6.56; P=0.0074) vs carriers of the 825CC genotype. The GNB3 genotype status did not affect responses to other acute and preventive therapeutic regimes including oxygen, verapamil, and corticosteroids, i.e., drugs not directly affecting G proteins. We conclude that pain relief by triptans is significantly modulated by a common genetic GNB3 variant.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Eletriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to elitriptan when treating (condition: cluster headache).	Details
Zolmitriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to zolmitriptan when treating (condition: cluster headache).	Details
Sumatriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to sumatriptan when treating (condition: cluster headache).	Details
Almotriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to almotriptan when treating cluster headache.	Details
Naratriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to naratriptan when treating (condition: cluster headache).	Details
Rizatriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to rizatriptan when treating (condition: cluster headache).	Details
Frovatriptan	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 Gene symbol: GNB3 UniProt: P16520	---	(T;T) / (C;T)	T Allele (rs5443)	Effect Directly Studied	Patients with this genotype have an increased likelihood of responding to frovatriptan when treating (condition: cluster headache).	Details