Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients.

Autor: Mehvari S; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Karimian Fathi N; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Saki S; Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Asadnezhad M; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Arzhangi S; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Ghodratpour F; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Mohseni M; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Zare Ashrafi F; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Sadeghian S; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Boroumand M; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Shokohizadeh F; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Rostami E; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Boroumand R; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Najafipour R; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Malekzadeh R; Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Riazalhosseini Y; McGill Genome Centre, Montreal, Quebec, Canada., Akbari M; Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada., Lathrop M; McGill Genome Centre, Montreal, Quebec, Canada., Najmabadi H; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Hosseini K; Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran., Kahrizi K; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.; McGill Genome Centre, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 Jun; Vol. 105 (6), pp. 611-619. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1111/cge.14491
Abstrakt: Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co-segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co-segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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