Dataset Information

Interaction between Sex and LDLR rs688 Polymorphism on Hyperlipidemia among Taiwan Biobank Adult Participants.

ABSTRACT: Hyperlipidemia is one of the strong risk factors for ischemic heart disease. Using the Taiwan Biobank (TWB) database, we evaluated the risk of hyperlipidemia and its interaction with sex and rs688 polymorphism on the low-density lipoprotein receptor (LDLR) gene. Data collection in the biobank started in 2008 and is ongoing. Data analysis was performed on the participants' data collected between 2008 and 2015. In general, 27.92% of the 9237 female participants and 32.65% of the 8690 male participants were identified with hyperlipidemia. Compared to the C/C genotype, C/T and T/T genotypes were not significant risk factors for hyperlipidemia (OR = 1.061, CI: 0.976-1.153 for C/T and OR = 1.052, CI: 0.845-1.309 for T/T genotype) in the general model. However, there was a significant interaction between sex and rs6888 on hyperlipidemia risk (p-interaction = 0.0321). With the male sex/CC genotype being the reference group, only the female sex/CT and T/T genotypes were closely associated with hyperlipidemia, with respective ORs of 1.153 (CI: 1.014-1.311) and 1.423 (CI: 1.056-1.917). Our data indicate that rs688 C/T and T/T genotypes may be associated with increased risk of hyperlipidemia in Taiwanese women. These findings may be relevant in lipid-modification therapy.

SUBMITTER: Liu YT

PROVIDER: S-EPMC7072141 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Interaction between Sex and LDLR rs688 Polymorphism on Hyperlipidemia among Taiwan Biobank Adult Participants.

Liu Yin-Tso YT Nfor Oswald Ndi ON Wang Lee L Hsu Shu-Yi SY Lung Chia-Chi CC Tantoh Disline Manli DM Wu Min-Chen MC Chang Horng-Rong HR Liaw Yung-Po YP

Biomolecules 20200205 2

Hyperlipidemia is one of the strong risk factors for ischemic heart disease. Using the Taiwan Biobank (TWB) database, we evaluated the risk of hyperlipidemia and its interaction with sex and rs688 polymorphism on the low-density lipoprotein receptor (LDLR) gene. Data collection in the biobank started in 2008 and is ongoing. Data analysis was performed on the participants' data collected between 2008 and 2015. In general, 27.92% of the 9237 female participants and 32.65% of the 8690 male particip ...[more]

PMID: 32033407

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Project description:BackgroundThe low-density lipoprotein receptor (LDLR) plays a significant role in maintaining the cellular cholesterol homeostasis. Mutations in the LDLR gene can lead to a significant rise in plasma LDL levels that may result in an increased risk of atherosclerosis and coronary heart disease. The purpose of this study was to assess the potential association of the LDLR rs688 polymorphism with cardiovascular disease (CVD) in patients with end-stage kidney disease (ESKD) undergoing hemodialysis.MethodsIn this case-control study the polymorphism was genotyped by the allele specific PCR method in 800 patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared in subgroups of patients with CVD (552) versus those without CVD (248).ResultsA significant difference was observed in genotype distribution among ESKD patients and healthy controls. The frequencies of the T allele and TT genotype in ESKD group were significantly higher, with OR (95% CI) 2.2 (1.87-2.6), p < 0.0001 and 5.84 (3.94-8.65), p < 0.0001, respectively. In the he ESKD cohort the distribution of the rs688 was compared between CVD+ and CVD- subgroups. A strong association of the polymorphism with the CVD risk was observed in this analysis. The frequencies of the T allele and TT genotype were significantly higher in CVD+ subgroup, with OR (95% CI) 3.4 (2.71-4.26), p < 0.0001 and 13.2 (7.87-22.09), p < 0.0001, respectively. A multivariate logistic regression analysis was performed to estimate the association between rs688 T variant and risk of CVD. After adjustment for age, sex, BMI, hypertension and diabetes, both CT and TT genotypes were associated with an increased risk of developing CVD in the dominant, recessive and codominant models of inheritance. No significant differences in serum LDL cholesterol levels were found when compared between genotypes.ConclusionsThe present study is the first to demonstrate the association of the LDLR gene polymorphism with increased susceptibility to cardiovascular disease in ESKD patients. This finding needs further investigation to confirm that LDLR rs688 might be a novel genetic risk factor with some prognostic capacity for CVD in ESKD patients.

Project description:ImportanceDetection of disease-associated variants in the BRCA1 and BRCA2 (BRCA1/2) genes allows for cancer prevention and early diagnosis in high-risk individuals.ObjectivesTo identify pathogenic and likely pathogenic (P/LP) BRCA1/2 variants in an unselected research cohort, and to characterize the features associated with P/LP variants.Design, setting, and participantsThis is a cross-sectional study of adult volunteers (n = 50 726) who underwent exome sequencing at a single health care system (Geisinger Health System, Danville, Pennsylvania) from January 1, 2014, to March 1, 2016. Participants are part of the DiscovEHR cohort and were identified through the Geisinger MyCode Community Health Initiative. They consented to a research protocol that included sequencing and return of actionable test results. Clinical data from electronic health records and clinical visits were correlated with variants. Comparisons were made between those with (cases) and those without (controls) P/LP variants in BRCA1/2.Main outcomesPrevalence of P/LP BRCA1/2 variants in cohort, proportion of variant carriers not previously ascertained through clinical testing, and personal and family history of relevant cancers among BRCA1/2 variant carriers and noncarriers.ResultsOf the 50 726 health system patients who underwent exome sequencing, 50 459 (99.5%) had no expected pathogenic BRCA1/2 variants and 267 (0.5%) were BRCA1/2 carriers. Of the 267 cases (148 [55.4%] were women and 119 [44.6%] were men with a mean [range] age of 58.9 [23-90] years), 183 (68.5%) received clinically confirmed results in their electronic health record. Among the 267 participants with P/LP BRCA1/2 variants, 219 (82.0%) had no prior clinical testing, 95 (35.6%) had BRCA1 variants, and 172 (64.4%) had BRCA2 variants. Syndromic cancer diagnoses were present in 11 (47.8%) of the 23 deceased BRCA1/2 carriers and in 56 (20.9%) of all 267 BRCA1/2 carriers. Among women, 31 (20.9%) of 148 variant carriers had a personal history of breast cancer, compared with 1554 (5.2%) of 29 880 noncarriers (odds ratio [OR], 5.95; 95% CI, 3.88-9.13; P < .001). Ovarian cancer history was present in 15 (10.1%) of 148 variant carriers and in 195 (0.6%) of 29 880 variant noncarriers (OR, 18.30; 95% CI, 10.48-31.4; P < .001). Among 89 BRCA1/2 carriers without prior testing but with comprehensive personal and family history data, 44 (49.4%) did not meet published guidelines for clinical testing.Conclusions and relevanceThis study found that compared with previous clinical care, exome sequencing-based screening identified 5 times as many individuals with P/LP BRCA1/2 variants. These findings suggest that genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remain undetected within health care systems and may provide opportunities to reduce morbidity and mortality in patients.

Project description:PURPOSE:The low-density lipoprotein receptor is responsible for the binding and uptake of plasma LDL particles and plays a critical role in maintaining cellular cholesterol homeostasis. LDLR gene SNP rs688 has been reported to be associated with increased plasma total and LDL cholesterol in several populations and can lead to elevated plasma LDL levels, resulting in an increased risk for atherosclerosis and coronary artery disease. This study aimed to explore genetic LDLR variant rs688 for its potential roles in coronary artery disease. METHODOLOGY:This study recruited 200 coronary artery disease patients and 200 healthy individuals. Genotyping of LDLR-rs688C > T gene variations was performed using the allele specific PCR method. Correlation of LDLR-rs688C > T gene variants with different clinicopathological features of coronary artery disease patients was performed. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the correlation of this microRNA polymorphism with coronary artery disease risk. RESULTS:A significant difference was observed in genotype distribution among the coronary artery disease and matched healthy controls (p = 0.003). The frequencies of all three genotypes CC, CT, TT reported in the patient samples were 14%, 65% and 21% and in the healthy controls samples were 18%, 73% and 9%, respectively. The increased risk of developing CAD in Indian patients was found to be associated with LDLR rs688 TT genotype (OR = 3.0, 95% CI, 1.43 × 6.2; p = 0.003) RR 1.87 (1.20?2.91) p = 0.0037) and also the increased risk of developing CAD was reported to be associated with LDLR rs688 T allele (OR = 0.74, 95% CI, 1.57?0.97; p = 0.03) RR 0.85 (0.73?0.99) p = 0.03) compared to the C allele. Therefore, it was observed that more than a 3.0- and 0.74-fold increase risk of developing CAD was associated with TT genotype and T allele in Indian coronary artery disease patients. CONCLUSION:The findings indicated that LDLR rs688 TT genotype and T allele are associated with an increased susceptibility to coronary artery disease patients. LDLR-rs688C > T gene variation can be used as a predisposing genetic marker for coronary artery disease. Further studies with larger sample sizes are necessary to confirm our findings.

Dataset Information

Interaction between Sex and LDLR rs688 Polymorphism on Hyperlipidemia among Taiwan Biobank Adult Participants.

Publications

Interaction between Sex and LDLR rs688 Polymorphism on Hyperlipidemia among Taiwan Biobank Adult Participants.

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