A substitution mutation in LRP8 gene is significantly associated with susceptibility to familial myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a multifactorial disease caused by the suspension of blood circulation in a part of the myocardium. Understanding the genetic basis of MI can provide insight regarding the pathogenesis of the disease. The aim of this study was to investigate the association between pathogenic mutations and early-onset MI in five families with familial MI and without common MI risk factor. METHODS: Patients with MI younger than 50 years with family history of MI and without common diagnostic criteria (obesity, diabetes, familial hypercholesterolemia, opium/alcohol use) were evaluated for pathogenic mutations by whole exome sequencing (WES) and mutation was confirmed by polymerase chain reaction (PCR)-Sanger sequencing. RESULTS: The c.2855G > A missense mutation with homozygous autosomal recessive inheritance was identified in low-density lipoprotein receptor-related protein 8 (LRP8) gene in all patients of a family. CONCLUSION: The c.2855G > A (R952Q) mutation in LRP8 gene in homozygous state could be considered as a possible etiology of early-onset familial MI.

Genetic analysis of early onset familial coronary artery diseases.

INTRODUCTION: Coronary artery diseases (CAD) are the most common causes of death. Myocardial infarction (MI) is a complex multifactorial and the most severe type of CAD. Early onset MI in a first-degree relative could be defined as an independent risk factor for CAD. This study was performed to investigate the genetic cause of early onset familial CAD. MATERIAL AND METHODS: In this study, the genetic cause of familial CAD was investigated in patients with a family history of CAD who underwent angiography before the age of 50 years. The patients did not have any diagnostic criteria for familial hypercholesterolemia, diabetes, or obesity, and also they were not opium or alcohol users. Whole exome sequencing in probands was performed and mutation was confirmed by PCR and Sanger sequencing. RESULTS: In our studied population, the c.501G>C (p.K167N) mutation in the OLR1 gene was identified in a family. Mutation was confirmed by PCR and Sanger sequencing in the homozygous state (GG) in patients. Healthy individuals in this family were heterozygous (GC) and homozygous (CC). CONCLUSIONS: This finding suggests that the OLR1 gene could be a possible cause of early onset familial MI. Considering that parents of all affected individuals had a consanguineous marriage, it is important to perform carrier screening and genetic counseling in this family and their close relatives as a prevention strategy in populations at risk.