The effect ofMVK-MMABvariants, their haplotypes and G×E interactions on serum lipid levels and the risk of coronary heart disease and ischemic stroke

Abstract

AimThis study aimed to detect the association of the mevalonate kinase (MVK) and methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) gene variants, their haplotypes, and gene-environment (G×E) interactions on serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Chinese Han population.MethodsGenotyping of the rs3759387, rs7134594, rs877710 and rs9593 SNPs in 846 CHD and 869 IS patients and 847 healthy controls was performed by PCR-RFLP and Sanger sequencing. Logistic regression and factor regression were used to investigate the association of 4 MVK-MMAB SNPs and serum lipid levels and the risk of CHD and IS.ResultsThe genotypic and allelic frequencies of the rs3759387 and rs7134594 SNPs differed between controls and patients (P < 0.0125-0.001). The rs3759387 SNP was associated with the risk of CHD and IS in different genetic models. The A-T-G-A and C-T-C-T haplotypes were associated with increased risk of CHD. The haplotype of A-T-G-A was associated with an increased risk of IS, whereas the C-T-G-A haplotype was associated with a decreased risk of IS. Interactions of C-T-C-T-smoking or C-T-C-T-age on the risk of CHD, and A-T-G-A-hypertension or A-T-G-A-age on the risk of IS were also observed. The subjects with the rs3759387AA genotype in controls had lower high-density lipoprotein cholesterol (HDL-C) levels than did the subjects with AC/CC genotypes. Several SNPs interacted with alcohol consumption and cigarette smoking to increase serum HDL-C and apolipoprotein A1 levels, but they interacted with body mass index ≥ 24 kg/m2 to decrease serum HDL-C and apolipoprotein A1 levels.ConclusionSeveral MVK-MMAB variants, especially the rs3759387 SNP, 4 main haplotypes, and G×E interactions were associated with serum lipid levels and the risk of CHD and IS in a Chinese Han population.

Association between the <i>MVK</i> rs2287218 SNP and the risk of coronary heart disease and ischemic stroke: A case-control study

“…Mutations in the MVK gave rise to hyperimmunoglobulinemia D syndrome (HIDS), in which low HDL-C levels could be found (16), in accordance with the latest GWAS findings (12,13). Several novel loci in MVK were confirmed to be associated with serum HDL-C levels (17)(18)(19) and an increased risk of CHD and IS (19). But no significant association between the MVK rs2287218 SNP and serum lipid levels was conducted by Sun et al in a Northern Chinese Han population (20).…”

“…The subjects with CT/TT genotypes of the MVK rs2287218 SNP contributed to the increased risk of CHD and IS. A previous study confirmed that the MVK rs3759387 AC/CC genotypes interacted with some environmental exposures (such as males, elder), resulting in increasing the risk of CHD and IS (19), which suggested gene-environment interactions contributed to higher risk of CHD and IS. It was reported that the MVK variants displayed low HDL-C levels and an activity decline of the MVK.…”

“…The associations between the MVK rs2338104 SNP and HDL-C levels were definitive (P < 0.001) and consistent (18,35). In addition, the MVK rs3759387AA genotype had lower HDL-C levels than the rs3759387AC/CC genotypes (19). Furthermore, MVK (i85G→T and S52NG→A) had low HDL-C levels linked to dietary habit, especially in carbohydrates intakes (17).…”

Genes associated with inflammation may serve as biomarkers for the diagnosis of coronary artery disease and ischaemic stroke

“…Currently, the diagnosis of CAD is based on ischaemiarelated symptoms, detailed physical examination, electrocardiogram changes, elevated biomarkers of myocardial injury and coronary angiography [32,33]. Meanwhile, the diagnosis of ischaemic stroke (IS) is also based on the patient's symptoms, signs, strict neurological examination SBP Systolic blood pressure, DBP Diastolic blood pressure, PP Pulse pressure, Glu Glucose, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, Apo Apolipoprotein, TC Total cholesterol, TG Triglyceride a Continuous data were presented as means ± SD and determined by two side t-test b A chi-square analysis was used to evaluate the difference of the rate between the groups and MRI scans [34]. However, the early diagnosis of CAD and IS is still limited.…”

LncRNA SNHG8 is identified as a key regulator of acute myocardial infarction by RNA-seq analysis

“…The blood samples were collected before PCI and just a few hours after chest pain occurred, and were very suitable for the development of early diagnosis biomarkers. Clinical data collection, biochemical measurements and diagnostic criteria were performed according to previous studies [27,28]. The Declaration of Helsinki of 1975 (http:// www.wma.net/en/30publications/10policies/b3/), which was revised in 2008, was followed, and the Ethics Committee of Liuzhou people's Hospital agreed with the study design (No: Lunshen-2017-KY; Mar.…”