LIPID PROFILE AND GENETIC MARKERS ASSOCIATED WITH THE LEVEL OF OXIDIzED LOW DENSITY LIPOPROTEIDES

Oxidatively modified low-density lipoproteins (oxLDL) play an important role in the occurrence and progression of atherosclerosis. To identify the genetic factors influencing the oxLDL levels, we have genotyped 776 DNA samples of Russian individuals for 196,725 single-nucleotide polymorphisms (SNPs) using the Cardio-MetaboChip (Illumina, USA) and conducted genome-wide association study (GWAS). Fourteen common variants in the locus including APOB gene were significantly associated with the oxLDL levels ( P < 2.18 × 10 −7 ). These variants explained only 6% of the variation in the oxLDL levels. Then, we assessed the contribution of rare coding variants of APOB gene to the oxLDL levels. Individuals with the extreme oxLDL levels (48 with the lowest and 48 with the highest values) were selected for targeted sequencing of the region including APOB gene. To evaluate the contribution of the SNPs to the oxLDL levels we used various statistical methods for the association analysis of rare variants: WST, SKAT, and SKAT-O. We revealed that both synonymous and nonsynonymous SNPs affected the oxLDL levels. For the joint analysis of the rare and common variants, we conducted the SKAT-C testing and found a group of 15 SNPs significantly associated with the oxLDL levels ( P = 2.14 × 10 −9 ). Our results indicate that the oxLDL levels depend on both common and rare variants of the APOB gene.

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“…Clinical and laboratory characteristics of the patients are shown in Table 1. Under oxLDL we mean the MDA-modified LDL [28].…”

Section: Resultsmentioning

confidence: 99%

“…Glyoxal and methylglyoxal, like MDA, can cause the atherogenic modification of LDL [4, 26, 27]. Previously we have determined that by using Oxidized LDL ELISA kit (Mercodia, Sweden) we can measure not any oxidized LDL, but mainly MDA-modified LDL (S1 Fig) [28]. Further under oxidatively modified LDL (oxLDL) we mean only these MDA-modified LDL.…”

Section: Methodsmentioning

confidence: 99%

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

et al. 2019

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Pathogenetic rationale for using an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and an antioxidant coenzyme Q<sub>10</sub> in the treatment and prevention of cardiovascular disease

Dzugkoev¹,

Garmash²,

Дзугкоева³

2021

Cardiovasc Ther Prev

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The review discusses atherosclerosis-related mechanisms of car-diovascular disease development, as well as the optimization of their prevention and treatment methods. Recent experimental and clinical studies have shown the important role of vascular endothelium in the development and progression of atherosclerosis. Myocardial ischemia, activation of free-radical processes and impaired bioenergetics initiate a decrease in production of nitric oxide, which plays major vasodilator role. In this regard, the scientists is interested in the search for new drugs that can affect the main pathogenetic links of coronary artery disease. Statins are currently the drugs of choice. However, they are not always effective and have an ambiguous effect on oxidative potential of myocardial cells and endothelial function. Moreover, inhibition of mevalonic pathway for cholesterol synthesis is accompanied by a deficiency of coenzyme Q10, which is the central cellular antioxidant that protects phospholipids of cell membranes from free radicals. Rationale of using coenzyme Q10 in the complex treatment and secondary prev ention of cardiovascular diseases, including coronary artery di sease, is discussed.

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LIPID PROFILE AND GENETIC MARKERS ASSOCIATED WITH THE LEVEL OF OXIDIzED LOW DENSITY LIPOPROTEIDES

Cited by 2 publications

References 8 publications

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

Multiple rare and common variants in APOB gene locus associated with oxidatively modified low-density lipoprotein levels

Pathogenetic rationale for using an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and an antioxidant coenzyme Q<sub>10</sub> in the treatment and prevention of cardiovascular disease

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