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Osteopontin Gene Polymorphisms Are Associated with Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease.

ABSTRACT: Osteopontin (OPN) is considered a clinical predictor of cardiovascular disease. We aimed to evaluate the association of the OPN gene polymorphisms rs2728127 and rs11730582 with the development of premature coronary artery disease (pCAD), cardiovascular risk factors, and cardiometabolic parameters. We evaluated 1142 patients with pCAD and 1073 controls. Both polymorphisms were determined by Taqman assays. Similar allele and genotype frequencies were observed in both groups; additionally, an association of these polymorphisms with CAD and cardiometabolic parameters was observed in both groups. In patients with pCAD, the rs11730582 was associated with a high risk of hypoadiponectinemia (OR = 1.300, P _additive = 0.003), low risk of hypertension (OR = 0.709, P _{codominant 1} = 0.030), and low risk of having high non-HDL cholesterol (OR = 0.637, P _additive = 0.038). In the control group, the rs2728127 was associated with a low risk of fatty liver (OR = 0.766, P _additive = 0.038); while the rs11730582 was associated with a low risk of hypoadiponectinemia (OR = 0.728, P _dominant = 0.022), and risk of having elevated apolipoprotein B (OR = 1.400, P _dominant = 0.031). Our results suggest that in Mexican individuals, the rs11730582 and rs2728127 OPN gene polymorphisms are associated with some abnormal metabolic variables in patients with pCAD and controls.

SUBMITTER: Perez-Hernandez N

PROVIDER: S-EPMC8615378 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Coronary artery disease (CAD) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. We analyzed whether interleukin-24 (IL-24) gene polymorphisms are associated with premature CAD in a case-control association study. Four polymorphisms (rs1150253, rs1150256, rs1150258, and rs3762344) of the IL-24 gene were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 952 patients with premature CAD, 284 individuals with subclinical atherosclerosis (SA), and 912 controls. The studied polymorphisms were not associated with the risk of premature CAD or SA (P>0.05). Under dominant models adjusted for age, sex, body mass index, and medication, the polymorphisms were associated with cardiometabolic parameters and cardiovascular risk factors. Three polymorphisms (rs1150253, rs1150256, and rs3762344) were associated with hypertension and increased levels of systolic blood pressure in controls. In SA, 2 polymorphisms (rs1150256 and rs3762344) were associated with type 2 diabetes mellitus, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase, whereas rs1150253 was associated with GGT and type 2 diabetes mellitus and rs1150258 with GGT and alkaline phosphatase. In premature CAD, the 4 polymorphisms were associated with total cholesterol >200?mg/dL, low-density lipoprotein cholesterol (LDL-C), and GGT, whereas rs1150256 was associated also with ApoA. On the other hand, rs1150258 was associated with ApoA, LDL-C >100?mg/dL, and apoB/apoA ratio, and rs3762344 with ApoA, apoB/apoA ratio, LDL-C >100?mg/dL, and total cholesterol. On the basis of single-nucleotide polymorphism functional prediction software, rs1150253 and rs1150258 polymorphisms seem to be functional. The 4 studied polymorphisms were in linkage disequilibrium and had a similar haplotype distribution in patients and controls. Our study demonstrates the association of IL-24 polymorphisms with metabolic and cardiovascular risk factors in individuals with premature CAD, SA, and controls.

Project description:BackgroundRecently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.MethodsWe enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.ResultsThe following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190-4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012-2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233-4.348, P = 0.015).ConclusionsAmong the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.

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Osteopontin Gene Polymorphisms Are Associated with Cardiovascular Risk Factors in Patients with Premature Coronary Artery Disease.

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