Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with left ventricular wall thickness in patients with hypertension.
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.
Nakagami
Hironori
H
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan. nakagami@gts.med.osaka-u.ac.jp
Kikuchi
Yasushi
Y
Katsuya
Tomohiro
T
Morishita
Ryuichi
R
Akasaka
Hiroshi
H
Saitoh
Shigeyuki
S
Rakugi
Hiromi
H
Kaneda
Yasufumi
Y
Shimamoto
Kazuaki
K
Ogihara
Toshio
T
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
C430866:CMYA5 protein, human; D009124:Muscle Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II