title: Floppy mitral valve/mitral valve prolapse syndrome: Beta-adrenergic receptor polymorphism may contribute to the pathogenesis of symptoms.
abstract: BACKGROUND
  Certain patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP) may have symptoms that cannot be explained on the severity of mitral valvular regurgitation (MVR) alone; hypersensitivity to adrenergic stimulation has been suggested in this group defined as the FMV/MVP syndrome.
  
  
  METHODS
  Ninety-eight patients (75 men, 23 women) with mitral valve surgery for FMV/MVP were studied. Of those 41 (42%) had symptoms consistent with FMV/MVP syndrome [29 men (39%), 12 women (52%)]; median age of symptom onset was 30 years (range 10-63 years) and median duration of symptoms prior to valve surgery was 16 years (range 3-50 years). Ninety-nine individuals (70 men, 29 women) without clinical evidence of any disease were used as controls. Genotyping of β1 and β2 adrenergic receptors was performed.
  
  
  RESULTS
  β-Adrenergic receptor genotypes (β1 and β2) were similar between control and overall FMV/MVP patients. Subgroup analysis of patients, however, demonstrated that the genotype C/C at position 1165 resulting in 389 Arg/Arg of the β1 receptor was more frequent in women compared to those without FMV/MVP syndrome and to normal control women (p<0.025). This polymorphism may be related to hypersensitivity to adrenergic stimulation as reported previously in these patients.
  
  
  CONCLUSIONS
  This study shows a large proportion of patients with FMV/MVP, predominantly women, had symptoms consistent with the FMV/MVP syndrome for many years prior to the development of significant MVR, and thus symptoms cannot be attributed to the severity of MVR alone. Further, women with FMV/MVP syndrome, symptoms at least partially may be related to β1-adrenergic receptor polymorphism, which has been shown previously to be associated with a hyperresponse to adrenergic stimulation.
authors.affiliation: Agios Lukas Hospital, Thessaloniki, Greece.
authors.forename: Efstratios K
authors.initials: EK
authors.lastname: Theofilogiannakos
authors.affiliation: The Ohio State University, Division of Cardiovascular Medicine, Columbus, OH, USA.
authors.forename: Konstantinos Dean
authors.initials: KD
authors.lastname: Boudoulas
authors.affiliation: University of Florida, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, Gainesville, FL, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gawronski
authors.affiliation: University of Florida, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, Gainesville, FL, USA.
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.affiliation: Agios Lukas Hospital, Thessaloniki, Greece.
authors.forename: Petros S
authors.initials: PS
authors.lastname: Dardas
authors.affiliation: Agios Lukas Hospital, Thessaloniki, Greece.
authors.forename: Vlasis
authors.initials: V
authors.lastname: Ninios
authors.affiliation: Agios Lukas Hospital, Thessaloniki, Greece.
authors.forename: Timotheos G
authors.initials: TG
authors.lastname: Kelpis
authors.affiliation: University of Florida, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, Gainesville, FL, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Agios Lukas Hospital, Thessaloniki, Greece.
authors.forename: Antonios A
authors.initials: AA
authors.lastname: Pitsis
authors.affiliation: The Ohio State University, Division of Cardiovascular Medicine, Columbus, OH, USA; Aristotelian University of Thessaloniki, Thessaloniki, Greece. Electronic address: boudoulas@bioacademy.gr.
authors.forename: Harisios
authors.initials: H
authors.lastname: Boudoulas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005838:Genotype; D006115:Greece; D006801:Humans; D008297:Male; D008875:Middle Aged; D008945:Mitral Valve Prolapse / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
chemical_list: D011943:Receptors, Adrenergic, beta
keywords: Beta-adrenergic receptor polymorphism; Floppy mitral valve; Mitral valve prolapse syndrome; Symptoms