Abstract P103: Genome-Wide Study of Gene Variants Associated with Differential Event Reduction by Pravastatin Therapy

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dov Shiffman ◽  
Stella Trompet ◽  
Judy Z Louie ◽  
Charles M Rowland ◽  
Joseph J Catanese ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Statin Therapy ◽  
Additive Model ◽  
The Elderly ◽  
Controlled Study ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Genome Wide Study

BACKGROUND : Statin therapy reduces the risk of coronary heart disease (CHD); however, the variability in response to statin therapy is not well understood. We investigated the effect of genetic variation on the reduction of CHD events by pravastatin therapy. METHODS : We genotyped 682 CHD cases from CARE and 383 CHD cases from WOSCOPS, two randomized placebo-controlled studies of pravastatin using the Illumina OMNI1 bead array. Single nucleotide polymorphisms (SNPs) that were associated with differential CHD event reduction by pravastatin therapy were investigated in PROSPER, a randomized placebo-controlled study of pravastatin in the elderly. RESULTS : A combined case-only analysis of CARE and WOSCOPS identified 62 SNPs associated with differential event reduction by pravastatin therapy (P int <0.0001 for interaction between treatment and genotype in an additive model). We investigated 57 of these SNPs in PROSPER. In an analysis that included cases as well as non-cases of CARE, WOSCOPS, and PROSPER, we found that for an intronic SNP in DNAJC5B (rs13279522), CHD event reduction by pravastatin therapy according to genotype differed in all 3 studies: P int =0.001 in CARE, P int =0.01 in WOSCOPS, P int =0.002 in PROSPER, and P int =3X10 -7 in a combined analysis of CARE, WOSCOPS and PROSPER (Figure). CONCLUSIONS : We have identified a SNP that is associated with differential event reduction by pravastatin therapy in CARE, WOSCOPS, and PROSPER. This SNP merits investigation in additional randomized studies of pravastatin and other statins.

scholarly journals Association of TIMP4 gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6270
Author(s):  
Jiaqi Wang ◽  
Feimeng An ◽  
Yuju Cao ◽  
Hongyan Gao ◽  
Mingqi Sun ◽  
...  
Keyword(s):  
Femoral Head ◽  
Additive Model ◽  
Northern China ◽  
Additive Models ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Link Type ◽  
Intravascular Thrombosis ◽  
Normal Individuals

BackgroundIn clinical treatment, the use of steroid hormones is an important etiological factor of non-traumatic osteonecrosis of the femoral head (ONFH) risk. As an endogenous inhibitor of matrix metalloproteinases (MMPs) in the extracellular matrix, the expression of tissue inhibitors of metalloprotease-4 (TIMP4) plays an essential role in cartilage and bone tissue damage and remodeling, vasculitis formation, intravascular thrombosis, and lipid metabolism.MethodsThis study aimed to detect the association between TIMP4 polymorphism and steroid-induced ONFH. We genotyped seven single-nucleotide polymorphisms (SNPs) in TIMP4 genes and analyzed the association with steroid-induced ONFH from 286 steroid-induced ONFH patients and 309 normal individuals.ResultsWe performed allelic model analysis and found that the minor alleles of five SNPs (rs99365,rs308952,rs3817004,rs2279750, andrs3755724) were associated with decreased steroid-induced ONFH (p = 0.02,p = 0.03,p = 0.04,p = 0.01,p = 0.04, respectively).rs2279750showed a significant association with decreased risk of steroid-induced ONFH in the Dominant and Log-additive models (p = 0.042,p = 0.028, respectively), andrs9935,rs30892, andrs3817004were associated with decreased risk in the Log-additive model (p = 0.038,p = 0.044,p = 0.042, respectively). In further stratification analysis, TIMP4 gene variants showed a significant association with steroid-induced ONFH in gender under the genotypes. Haplotype analysis also revealed that “TCAGAC” and “CCGGAA” sequences have protective effect on steroid-induced ONFH.ConclusionOur results indicate that five TIMP4 SNPs (rs99365,rs308952,rs3817004rs2279750, andrs3755724) are significantly associated with decreased risk of steroid-induced ONFH in the population of northern China.

scholarly journals A Replication Study from Chinese Supports Association between Lupus-Risk Allele inTNFSF4and Renal Disorder

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Xu-jie Zhou ◽  
Fa-juan Cheng ◽  
Yuan-yuan Qi ◽  
Ming-hui Zhao ◽  
Hong Zhang
Keyword(s):  
Lupus Nephritis ◽  
Renal Biopsy ◽  
Chinese Population ◽  
Renal Involvement ◽  
Additive Model ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Renal Disorder ◽  
Risk Alleles ◽  
Genome Wide

A recent phenotypic association study of genetic susceptibility loci in SLE suggested thatTNFSF4gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes andTNFSF4expression were determined. The stainings ofTNFSF4in renal biopsy specimens were checked by immunohistochemistry. The SNPs ofTNFSF4were associated with renal involvement in lupus patients from the Chinese population (Pvalues for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (P=0.034). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lowerTNFSF4expression. StrongTNFSF4expression was detected in lymph nodes and “apparently normal” paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data,TNFSF4was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association ofTNFSF4with renal disorder in SLE patients in the Chinese population, which supported thatTNFSF4may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed.

A Genome-Wide Study of Single-Nucleotide Polymorphisms in MicroRNAs and Further In Silico Analysis Reveals Their Putative Role in Susceptibility to Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 58 (1) ◽  
pp. 55-64
Author(s):  
Soraya Herrera-Espejo ◽  
Borja Santos-Zorrozua ◽  
Paula Alvarez-Gonzalez ◽  
Idoia Martin-Guerrero ◽  
Marian M. de Pancorbo ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
In Silico ◽  
Late Onset ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Silico Analysis ◽  
Genome Wide Study

Statin-induced adverse effects – facts and genes

2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh
Keyword(s):  
Risk Factors ◽  
Single Nucleotide Polymorphisms ◽  
Adverse Effects ◽  
Adverse Events ◽  
Statin Therapy ◽  
Significant Proportion ◽  
Gene Mutations ◽  
Nucleotide Polymorphisms ◽  
Serious Adverse Events ◽  
Single Nucleotide

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.

EpiPen: An R Package to Investigate Two-Locus Epistatic Models

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
Raymond K. Walters ◽  
Charles Laurin ◽  
Gitta H. Lubke
Keyword(s):  
Power Analysis ◽  
R Package ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Epistatic Interactions ◽  
Model Interpretation ◽  
Genome Wide ◽  
Using Data ◽  
Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, EpiPen, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. EpiPen facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

scholarly journals Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 363
Author(s):  
Sulochana K. Wasala ◽  
Dana K. Howe ◽  
Louise-Marie Dandurand ◽  
Inga A. Zasada ◽  
Dee R. Denver
Keyword(s):  
Genetic Variation ◽  
Potato Production ◽  
Globodera Pallida ◽  
Fixation Index ◽  
Parasitic Nematodes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Field Samples ◽  
Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study

2019 ◽  
pp. 204748731989467 ◽  
Author(s):  
Liu Miao ◽  
Guo-Xiong Deng ◽  
Rui-Xing Yin ◽  
Rong-Jun Nie ◽  
Shuo Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Plasma Homocysteine ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Artery Disease

Background Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction. Methods A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” ( n = 184,305) and “acute myocardial infarction” ( n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10–8, were used as an instrumental variable. Results None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction ( p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy ( p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction. Conclusions The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

Sign in / Sign up

Export Citation Format

Share Document