Catechol-O-Methyltransferase (COMT) rs4680 Val158Met Polymorphism is Associated with Widespread Pressure Pain Sensitivity and Depression in Women with Chronic, but not Episodic, Tension Type Headache

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The aims of this study were: 1, to investigate the association between the rs4680 Val158Met polymorphism in frequent episodic (FETTH) and chronic (CTTH) tension-type headache; and 2, to analyse the association between the rs4680 Val158Met polymorphism with clinical, psychological, or psychophysical variables.


Fifty women with FETTH, 50 with CTTH, and 50 matched healthy women participated. After amplifying Val158Met polymorphism by polymerase chain reaction, the genotype frequencies and allele distributions based on restriction fragment length polymorphism were assessed. Participants were classified according to the Val158Met polymorphism rs4680 genotype (Val/Val, Val/Met, or Met/Met). A headache diary collected clinical features. Disability (Headache Disability Inventory), sleep quality (Pittsburgh Sleep Quality Index), and depression/anxiety levels (Hospital Anxiety and Depression Scale) were also assessed. Pressure pain thresholds (PPT) were assessed bilaterally over the temporalis, upper trapezius, second metacarpal, and tibialis anterior by a blinded assessor.


The distribution of rs4680 Val158Met genotype was not significantly different between women with/without headache (P=0.796). No differences in headache features, disability, anxiety, and sleep quality were observed depending on the rs4680 Val158Met genotype. Women with CTTH, but not FETTH, carrying the Met/Met genotype had lower widespread PPTs and higher depressive symptoms than those with Val/Val or Val/Met genotype (P<0.05).


The Val158Met polymorphism (rs4680) does not appear to be involved in predisposition to suffer from tension-type headache; however, this genetic factor may be involved in the pathogenesis expression of CTTH, as greater pressure pain sensitivity and higher depressive levels were found in CTTH carrying the Met/Met genotype.

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