Low-density lipoprotein receptor gene mutation at Exon 2 and 4 in premature coronary artery disease in our population: LDLR gene mutation in premature coronary artery disease

Objective: To determine the frequency of mutations in Low density lipoprotein receptor gene at exon 2 and 4 and its association with premature coronary artery disease (PCAD).

Methods: A case-control study was conducted at Armed Forces Institute of Cardiology and Chemical Pathology department of Army Medical College Rawalpindi for a period of six months from June 2017 to December 2017. A sample size of 50 (40 patients, 10 controls) with 5% significance and 95% confidence interval was calculated with 4:1 case to control ratio. Consecutive sampling was used for distribution of participants into both groups. Diagnosed patients of premature coronary artery disease that is any cardiac event before the age of 45 in males and 50 in females were taken as cases. Controls were healthy males less than 45 years of age and females less than 50 years. Patients with diabetes mellitus, thyroid illnesses, any acute infection, low white blood cells count and kidney disorders were excluded. A total of fasting 10ml blood was withdrawn from each patient. 5ml was utilized for the routine blood tests and the rest 5ml was used for further genetic analysis.

Results: Total 50 participants were included in study. Mean age of participants in years was 42.48 ± 4.02 SD. Mean total cholesterol (TC) (mmol/l) were higher among cases (4.91±0.64 SD) than controls (4.22±0.66 SD). Serum triglyceride(Tg) (mmol/l) and low-density lipoprotein(LDL) (mmol/l) was also high among cases (2.07±0.58; 2.84±0.46) than controls (1.99±0.24; 1.98±0.32). One synonymous mutation in exon 2 of low-density lipoprotein receptor gene (LDLR) and one non-synonymous mutation in exon 4 (LDLR gene) were identified in our population in four patients among the forty cases. Data was analyzed by Statistical Package for the Social Science (SPSS) 21 version and a p-value of less than 0.05 was taken as significant.

Conclusion: Glutamic acid (E) is replaced by Lysine (K) at position number 207 (E207K) mutation at exon 4 of low-density lipoprotein receptor (LDLR) gene may be the causative genetic basis of premature coronary artery disease among Pakistani population. The identified synonymous mutation at exon 2 was not causative as there is no change in the amino acid.