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Hypermethylation and reduced expression of lipoprotein metabolism genes ABCG1, LIPC and PLTP in Obese and Diabetic subjects: Potential risk factors for Coronary artery disease

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Title Hypermethylation and reduced expression of lipoprotein metabolism genes ABCG1, LIPC and PLTP in Obese and Diabetic subjects: Potential risk factors for Coronary artery disease
 
Creator Indumathi, Bobbala
Oruganti, Sai Satish
Sharma, Gunjan
Kutala, Vijay Kumar
 
Subject ATP binding cassette transporter G1 (ABCG1)
Coronary artery disease (CAD)
Diabetes
Hepatic lipase (LIPC)
DNA methylation
Obesity
Phospholipid transfer protein (PLTP)
Smoking
 
Description 517-525
Increased lipid levels in the body can cause a plethora of complications and the lipoprotein metabolism genes such as
ATP binding cassette transporter G1 (ABCG1), hepatic lipase (LIPC) and phospholipid transfer protein (PLTP) have a key
role in the efflux of cholesterol from peripheral tissues to the liver. Altered methylation and expression of these genes in
obese individuals and patients with diabetes mellitus can increase the risk of coronary artery disease (CAD). Here, we
investigated the relationship of promoter methylation and expression of these lipoprotein metabolism genes ABCG1, LIPC
and PLTP with the risk of CAD in diabetes and obese subjects. The study group consisting of 574 subjects, including 207
angiographically confirmed CAD patients, 100 diabetic patients and 82 obesity subjects without CAD and 185 healthy
controls. DNA methylation status of ABCG1, LIPC and PLTP gene loci was determined by methylation-specific PCR and
gene expression was analysed by real-time PCR. In obese individuals, the hypermethylation of ABCG1 (OR = 3.83, 95%
CI = 2.11–6.96, P =0.0001) and PLTP (OR = 1.88, 95% CI = 1.07–3.28, P = 0.02 versus control) and reduced expression of
ABCG1 (0.4-fold) and PLTP (decreased by 0.0025-fold) were observed. Hypermethylation of ABCG1 (OR = 1.71, 95%
CI = 1.14–2.55, P = 0.01) and LIPC (OR = 1.58, 95% CI = 1.06–2.36, P = 0.02) genes was significantly higher in CAD
patients when compared to healthy controls, whereas reduced expression of these genes by 0.77- and 0.82-fold was
observed. The hypermethylation of LIPC was observed in CAD subjects with higher cholesterol and LDL (low density
lipoproteins) levels (OR = 2.2, 95% CI = 1.18–4.09, P = 0.01; OR = 2.08, 95% CI = 1.12–4.22, P = 0.02, respectively).
CAD subjects with diabetes (n=118) showed hypermethylation of LIPC (OR = 2.1, 95% CI = 1.2–3.67, P = 0.01) and PLTP
(OR = 2.01, 95% CI = 1.13–3.59, P = 0.01). Hypermethylation of ABCG1 (OR = 1.91, 95% CI = 1.09–3.36, P = 0.03) and
LIPC (OR = 2.0, 95% CI = 1.12–3.55, P = 0.02) genes were associated with lifestyle habit such as cigarette smoking. The
results suggest that obese individuals are at a risk of CAD through alteration of lipoprotein homeostasis. Lifestyle
modifications such as reduction in BMI and cessation of cigarette smoking might reduce the risk of CAD.
 
Date 2023-06-30T05:42:03Z
2023-06-30T05:42:03Z
2023-06
 
Type Article
 
Identifier 0975-1009 (Online); 0019-5189 (Print)
http://nopr.niscpr.res.in/handle/123456789/62215
https://doi.org/10.56042/ijeb.v61i07.2212
 
Language en
 
Publisher NIScPR-CSIR, India
 
Source IJEB Vol.61(07) [July 2023]