The C-allele of tissue inhibitor of metalloproteinases 2 is associated with increased magnitude of QT dispersion prolongation in elderly Chinese - 4-year follow-up study.
BACKGROUND
Matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) trigger the signal cascade instigating cardiac remodeling and fibrosis, which lead to changes of repolarization variables. We investigate the influence of MMP9-1562 C/T and TIMP2-418 G/C gene polymorphisms on repolarization parameters including QT dispersion (QTd) and the peak and the end of the T wave interval (Tpe) in a prospective cohort.


METHODS
Of 1500 people screened, 106 elderly Chinese without organic heart disease were recruited and received electrocardiography at the baseline, second and 4th year follow-ups. The QTc (corrected QT), QTd, QTc dispersion (QTcd) and Tpe were manually calculated.


RESULTS
Age was 72.7+/-4.1 y (range 62-81 y). QTd, QTcd and Tpe were significantly prolonged (all p <0.001 at the 2nd and 4th year). At the 4th year the magnitude of QTd prolongation but not Tpe was significantly higher in subjects carrying the TIMP2 C-allele than non C-allele carriers (p=0.033) as well as QTcd (p=0.010). This association was still significant in multivariate analyses (p=0.012 and p=0.003 for QTd and QTcd, respectively) but not in MMP9 genotype.


CONCLUSIONS
The elderly Chinese with TIMP2 C-allele have higher magnitude of QTd and QTcd prolongation.
Lin
Tsung-Hsien
TH
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Chiu
Herng-Chia
HC
Lee
Ya-Ting
YT
Su
Ho-Ming
HM
Juo
Suh-Hang Hank
SH
Voon
Wen-Chol
WC
Lai
Wen-Ter
WT
Sheu
Sheng-Hsiung
SH
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D004562:Electrocardiography; D004791:Enzyme Inhibitors; D005500:Follow-Up Studies; D006801:Humans; D008133:Long QT Syndrome / Q000208:ethnology / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000037:antagonists & inhibitors / Q000235:genetics
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9