LINKAGE ANALYSIS BY A TRANSMISSION / DISEQUILIBRIUM TEST OF RUSSIAN SIBLING PAIRS WITH CORONARY ARTERY DISEASE
Tupitsina TV1,*, Slominsky PA1, Yufereva YM2, Perova NI2, Aronov DM2, Limborska SA1
*Corresponding Author: *Corresponding Author: Dr. Tatiana V. Tupitsina, Department of Human Molecular Genetics, Institute of Molecular Genetics of Russian Academy of Sciences, Kurchatov sq. 2, 123182, Moscow, Russia; Tel.: +007-499-1960210; Fax: +007-499-1960221; E-mail: tanya_tupitsina@mail.ru
page: 43

Abstract

We studied the association between coronary artery disease (CAD) and polymorphisms of the ABCA1, ACE, AGT, eNOS and EFNB3 genes in 85 Russian patients with angiography-proven CAD and 100 of their siblings. No gene analyzed had a z-score value of more than 2.47 for CAD or for its main clinical presentations due to sibling transmission/disequilibrium test (S-TDT). However, the DD genotype of ACE is significantly more prevalent in siblings with CAD [p = 0.025, relative risk (RR) 2.8], angina (p = 0.028, RR = 3.3) and myocardial infarction (MI) (p = 0.018, RR = 5.5). An increased risk of CAD, and its main manifestations, was associated with the R1587 allele of the ABCA1 gene:the RR for developing CAD was 4.88, for MI 6.18, and for angina 3.69 for siblings who were carriers of the R1587R and R1587K genotypes. Index of stenosis was significantly higher in probands with the K219K and R219K genotypes (p = 0.001). The combination of genotype K219K with R219K was more frequent among siblings with CAD (p = 0.044,RR = 2.38), arterial hypertension (p = 0.023, RR =2.87) and angina (p = 0.027, RR = 3.3). Thus, none of the genes studied can be considered as the maingene associated with CAD. However, the insertion/deletion (I/D) polymorphism of the ACE gene and the R219K and R1587K variants of ABCA1 are associated with a higher likelihood of developing CAD, MI and angina among Russians who have siblings affected by CAD.

Key words: Candidate genes; Coronary artery disease (CAD); Polymorphism; Risk factor; Siblings; Transmission/disequilibrium test




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