title: Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension.
abstract: We examined a gene polymorphism of a novel Z-disc-related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload.
authors.affiliation: Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan. nakagami@gts.med.osaka-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akasaka
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: C430866:CMYA5 protein, human; D009124:Muscle Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II