Association of brain-derived neurotrophic factor gene Val66Met polymorphism with primary dysmenorrhea.

Lin-Chien Lee,Li-Fen Chen,Jen-Chuen Hsieh,Ming-Wei Lin,Hsiang-Tai Chao,Horng-Der Shen,Cheng-Hao Tu,Reiner A Veitia

doi:10.1371/journal.pone.0112766

Abstract

Primary dysmenorrhea (PDM), the most prevalent menstrual cycle-related problem in women of reproductive age, is associated with negative moods. Whether the menstrual pain and negative moods have a genetic basis remains unknown. Brain-derived neurotrophic factor (BDNF) plays a key role in the production of central sensitization and contributes to chronic pain conditions. BDNF has also been implicated in stress-related mood disorders. We screened and genotyped the BDNF Val66Met polymorphism (rs6265) in 99 Taiwanese (Asian) PDMs (20–30 years old) and 101 age-matched healthy female controls. We found that there was a significantly higher frequency of the Met allele of the BDNF Val66Met polymorphism in the PDM group. Furthermore, BDNF Met/Met homozygosity had a significantly stronger association with PDM compared with Val carrier status. Subsequent behavioral/hormonal assessments of sub-groups (PDMs = 78, controls = 81; eligible for longitudinal multimodal neuroimaging battery studies) revealed that the BDNF Met/Met homozygous PDMs exhibited a higher menstrual pain score (sensory dimension) and a more anxious mood than the Val carrier PDMs during the menstrual phase. Although preliminary, our study suggests that the BDNF Val66Met polymorphism is associated with PDM in Taiwanese (Asian) people, and BDNF Met/Met homozygosity may be associated with an increased risk of PDM. Our data also suggest the BDNF Val66Met polymorphism as a possible regulator of menstrual pain and pain-related emotions in PDM. Absence of thermal hypersensitivity may connote an ethnic attribution. The presentation of our findings calls for further genetic and neuroscientific investigations of PDM.

Highlights

Primary dysmenorrhea (PDM), defined as pain associated with menstruation in the absence of organic disease, affects 90% of adolescent girls and more than 50% of menstruating women worldwide [1,2,3,4]
Demographic Characteristics (Table 1) There were no significant differences between the PDM and control groups in age, age at menarche, years of menstruating or average days of one menstrual cycle (P.0.05)
The interaction between the Brain-derived neurotrophic factor (BDNF) genotype and menstrual cycle for Beck Anxiety Inventory scores in the PDM group was not substantial, we found an effect of the gene (BDNF genotype) 6environment interaction on the Beck Anxiety Inventory scores when considering menstrual pain as an environmental stressor

Summary

Introduction

Primary dysmenorrhea (PDM), defined as pain associated with menstruation in the absence of organic disease, affects 90% of adolescent girls and more than 50% of menstruating women worldwide [1,2,3,4]. Despite the unclear pathogenesis of PDM, myometrial hypercontractility and vasoconstriction are the two most widely accepted mechanisms [5,6]. PDM can be associated with hampered daily function [11], decreased self-rated overall health [12], and negative moods (e.g., depressive and anxious symptoms) [13,14]. To our knowledge there is no report in the literature discussing possible genetic causes of PDM in terms of the pain experience and associated emotions

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Discussion

Conclusion