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
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Creator |
Indumathi, Bobbala
Oruganti, Sai Satish Sharma, Gunjan Kutala, Vijay Kumar |
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Subject |
ATP binding cassette transporter G1 (ABCG1)
Coronary artery disease (CAD) Diabetes Hepatic lipase (LIPC) DNA methylation Obesity Phospholipid transfer protein (PLTP) Smoking |
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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. |
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Date |
2023-06-30T05:42:03Z
2023-06-30T05:42:03Z 2023-06 |
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Type |
Article
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Identifier |
0975-1009 (Online); 0019-5189 (Print)
http://nopr.niscpr.res.in/handle/123456789/62215 https://doi.org/10.56042/ijeb.v61i07.2212 |
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Language |
en
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Publisher |
NIScPR-CSIR, India
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Source |
IJEB Vol.61(07) [July 2023]
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