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Heterozygosity in LDLR rs2228671 and rs72658855 Gene is Associated with Increased Risk of Developing Coronary Artery Disease in India –A Case-Control Study

Author(s):

Chandan K. Jha, Rashid Mir*, Shaheena Banu, Imadeldin Elfaki and Sukh Mohinder Singh Chahal   Pages 1 - 11 ( 11 )

Abstract:


Objective: Coronary artery disease (CAD) is one of the most common causes of death worldwide. Risk factors of CAD include high LDL-C, low high density lipoprotein (HDL), hypertension, and lack of exercise, genetic factors and others. Polymorphisms of LDLR gene have been associated with CAD in previous studies.

Methodology: The LDLR-rs72658855 C>T genotyping was detected by using allele-specific PCR (AS-PCR) .The association of the rs2228671 and rs72658855 with CAD in a south Indian cohort (200 CAD patients and 200 matched healthy controls was studied.

Results: Our findings showed that rs2228671 gene variability is associated with an increased susceptibility to coronary artery disease in codominant inheritance model for variant CC vs. CT OR 3.42(1.09-10.7),P<0.034 . A non-significant association was reported in recessive inheritance model for variant (CC+CT) vs. TT OR 0.56(0.16-1.95), P<0.36. and in dominant inheritance model for variant CC vs. (CT+TT) OR 2.8(1.07-7.34),P<0.032 .In case of allelic comparison, it was indicated that the LDLR rs2228671-T allele was associated with an increased risk of developing risk of CAD compared to C allele OR=2.4, 95% CI (1.05-5.64) P< 0.036 .Our findings showed that LDLR rs72658855 C>T gene variability is associated with an increased susceptibility to coronary artery disease in codominant inheritance model for variant CC vs. CT OR 1.7(1.1-2.6), P<0.015 and in dominant inheritance model for variant CC vs. (CT+TT) OR 1.66(1.07-2.58),P<0.0.02. A non-significant association was reported in recessive inheritance model for variant (CC+CT) vs. TT OR 0.56(0.16-1.95), P<0.36. In case of allelic comparison, a non-significant association was reported in LDLR rs72658855-T and C allele .

Conclusion: We concluded that the heterozygosity in LDLR-rs72658855and rs2228671 and T allele in LDLR rs2228671are strongly associated with an increased susceptibility to coronary artery disease. These results must be validated in future well-designed studies with larger sample sizes and different populations.

Keywords:

Coronary Artery Disease (CAD), Low-Density Lipoprotein Receptor (LDLR), Hypercholesterolemia, Atherosclerosis, Myocardial Infarction, Peripheral Arterial Disease (PAD)

Affiliation:

Department of Human Genetics, Punjabi University, Punjab 147002, Department of Medical Lab Technology, Prince Fahd Bin Sultan Research Chair, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Sri Jayadeva Institute of Cardiovascular science and Research, Bangalore, Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Department of Human Genetics, Punjabi University, Punjab 147002



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