Genetic analysis of early onset familial coronary artery diseases

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology

Background:

• Coronary artery diseases (CAD) are a leading cause of mortality worldwide.
• Myocardial infarction (MI), a severe form of CAD, can be influenced by genetic factors, particularly early onset in relatives.
• Familial hypercholesterolemia, diabetes, obesity, and substance use were excluded in this study population.

Purpose of the Study:

• To investigate the genetic underpinnings of early-onset familial coronary artery disease (CAD).
• To identify specific gene mutations associated with premature myocardial infarction (MI) in affected families.

Main Methods:

• Whole exome sequencing was performed on probands with a family history of CAD and angiography before age 50.
• Identified mutations were confirmed using polymerase chain reaction (PCR) and Sanger sequencing.
• Study population excluded individuals with familial hypercholesterolemia, diabetes, obesity, and substance use.

Main Results:

• The c.501G>C (p.K167N) mutation in the OLR1 gene was identified in a family with early-onset familial CAD.
• Affected individuals were homozygous for the mutation (GG), while healthy relatives were heterozygous (GC) or homozygous (CC).
• Mutation confirmation was achieved through PCR and Sanger sequencing.

Conclusions:

• The OLR1 gene mutation is a potential cause of early-onset familial myocardial infarction (MI).
• Consanguineous marriages in affected families highlight the importance of genetic factors.
• Carrier screening and genetic counseling are crucial preventive strategies for at-risk populations and families.