Dataset Information

Data to genetic risk assessment on high-density cholesterol level associated polymorphisms in Hungarian general and Roma populations.

ABSTRACT: Data obtained by genotyping single nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C) levels were utilized in Genetic Risk Score [unweighted (GRS) and weighted (wGRS)] computation on Hungarian general and Roma populations. The selection process of the SNPs as well as the results obtained are published in our research article (Piko et al., 2017) [1]. Linkage analyses were performed by study groups. Study populations were stratified by quintiles of weighted Genetic Risk Score. Multivariate linear regression analyses were performed using Genetic Risk Scores and HDL-C levels as dependent variables; and ethnicity, sex and age as independent variables. The study subjects were categorized into quintiles according their wGRS values. Associations of Genetic Risk Scores with plasma HDL-C levels (as a continuous variable) were observed in both populations. Finally, the two populations were merged and analyzed together by multivariate logistic regression where reduced plasma HDL-C level was the dependent variable; while ethnicity, age and sex were the independent ones.

SUBMITTER: Piko P

PROVIDER: S-EPMC5545818 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Data to genetic risk assessment on high-density cholesterol level associated polymorphisms in Hungarian general and Roma populations.

Pikó Péter P Fiatal Szilvia S Kósa Zsigmond Z Sándor János J Ádány Róza R

Data in brief 20170726

Data obtained by genotyping single nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C) levels were utilized in Genetic Risk Score [unweighted (GRS) and weighted (wGRS)] computation on Hungarian general and Roma populations. The selection process of the SNPs as well as the results obtained are published in our research article (Piko et al., 2017) [1]. Linkage analyses were performed by study groups. Study populations were stratified by quintiles of weighted Gen ...[more]

PMID: 28795114

Similar Datasets

Project description:Diabetes mellitus is a major public health problem with a wide range of prevalence among different ethnic groups. Early recognition of pre-diabetes is important to prevent the development of the disease, its complications, co-morbidities, and consequently early death. Insulin resistance (IR) is considered a condition that precedes type 2 diabetes; thus, understanding its underlying causes (genetic and non-genetic factors) will bring us closer to preventing it. The present study aimed to investigate the genetic susceptibility to IR and its impact on estimated longevity in populations with different ethnic origins using randomly selected samples of 372 Hungarian general (HG, as a reference with Caucasian origin) and 334 Roma participants (largest ethnic minority in Europe, with a northern India origin). In the present study, we used the Homeostasis Model Assessment—Insulin Resistance (HOMA—IR) to identify people with IR (>3.63) at the population level. To investigate the genetic predisposition to IR, 29 single nucleotide polymorphisms (SNPs) identified in a systematic literature search were selected and genotyped in sample populations. In the analyses, the adjusted p < 0.0033 was considered significant. Of these 29 SNPs, the commutative effects of 15 SNPs showing the strongest association with HOMA—IR were used to calculate an optimized genetic risk score (oGRS). The oGRS was found nominally significantly (p = 0.019) higher in the Roma population compared to HG one, and it was more strongly correlated with HOMA—IR. Therefore, it can be considered as a stronger predictor of the presence of IR among the Roma (AUCRoma = 0.673 vs. AUCHG = 0.528). Furthermore, oGRS also showed a significant correlation with reduced estimated longevity in the Roma population (β = −0.724, 95% CI: −1.230−−0.218; p = 0.005), but not in the HG one (β = 0.065, 95% CI: −0.388−0.518; p = 0.779). Overall, IR shows a strong correlation with a genetic predisposition among Roma, but not in the HG population. Furthermore, the increased genetic risk of Roma is associated with shorter estimated longevity, whereas this association is not observed in the HG one. Increased genetic susceptibility of Roma to IR should be considered in preventive programs targeting the development of type 2 diabetes, which may also reduce the risk of preventable premature death among them.

Project description:ImportanceLittle is known about the heterogeneity in low-density lipoprotein cholesterol levels (LDL-C) lowering with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor medications.ObjectiveTo evaluate the interindividual variability in LDL-C reduction with the PCSK9 inhibitor drug evolocumab.Design, setting, and participantsWe examined the percentage change in LDL-C levels from baseline in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, a placebo-controlled randomized clinical trial of the PCSK9 inhibitor evolocumab in patients with stable atherosclerotic cardiovascular disease who were taking statin medications. Patients in either treatment arm who had high baseline LDL-C variability during screening and either did not receive the study drug, altered their background lipid-lowering therapy regimen, or had no LDL-C level sample in week 4 were excluded from the primary analysis. Analyses in the patients were stratified by treatment arm. Data was collected from 2013 to 2016, and data were analyzed from January 2018 to November 2018.Main outcomes and measuresInterindividual variation in percent reduction in LDL-C with evolocumab.ResultsThere were 27 564 individuals in the cohort; after exclusions for baseline variability (n = 3524) or alterations in background lipid therapy and other causes (n = 2272), 21 768 patients remained. At week 4, the median percent reduction in LDL-C levels from baseline was 66% (interquartile range, 54%-76%; median [interquartile range] baseline value, 90 [79-105] mg/dL; postchange value, 31 [21-44] mg/dL) with evolocumab. During the first year, a total of 10 325 of 10902 patients in the evolocumab group (94.7%) had a reduction 50% or greater in LDL-C levels, 10 669 of 10 902 (97.9%) had a reduction 30% or more, and 10 849 of 10 902 (99.5%) had any reduction in LDL-C levels. Fifty-three patients (0.5%) had no apparent reduction in LDL-C levels. In the placebo arm, the median LDL-C reduction was 4% (interquartile range, 6% increase to 13% reduction; baseline median [IQR] value, 90 [79-106] mg/dL; postchange value, 87 [74-103] mg/dL) at 4 weeks. Waterfall plots showed notable variability in the top and bottom 5% of patients for both evolocumab and placebo groups, with large changes in LDL-C levels in the placebo group (increases of ≥25%, 531 patients [4.9%]; decreases of ≥25%, 985 patients [9.1%]). At 4 weeks, the placebo-adjusted reductions in LDL-C levels with evolocumab were 50% or greater in 9839 of 10 866 patients (90.5%) and 30% or greater in 10 846 of 10 866 patients (99.8%). Results were consistent across clinically relevant subgroups.Conclusions and relevanceThere appears to be a highly consistent robust reduction in LDL-C levels with evolocumab use.Trial registrationClinicalTrials.gov identifier: NCT01764633.

Dataset Information

Data to genetic risk assessment on high-density cholesterol level associated polymorphisms in Hungarian general and Roma populations.

Publications

Data to genetic risk assessment on high-density cholesterol level associated polymorphisms in Hungarian general and Roma populations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure