Abstract:
OBJECTIVE:Genetic polymorphisms are associated with lipid-lowering response to statins, but generalizeability to disease endpoints is unclear. The association between 82 common single nucleotide polymorphisms (SNPs) in six lipid-related or statin-related genes (ABCB1, CETP, HMGCR, LDLR, LIPC, NOS3) and incident nonfatal myocardial infarction (MI) and ischemic stroke was analyzed according to current statin use and overall in a population-based case-control study (856 MI, 368 stroke, 2686 controls). METHODS:Common SNPs were chosen from resequencing data using pairwise linkage disequilibrium. Gene-level analyses (testing global association within a gene) and SNP-level analyses (comparing the number of observed vs. expected associations across all genes) were performed using logistic regression, setting nominal statistical significance at P value of less than 0.05. RESULTS:No gene-level interactions with statin use on MI or stroke were identified. Across all genes, two SNP-statin interactions on MI were observed (one ABCB1, one LIPC) and five interactions on stroke (one CETP, four LIPC). The strongest SNP-statin interaction was for synonymous CETP SNP rs5883 on stroke (P=0.008). Gene-level associations were present for LIPC and MI (P=0.026), but not other genes or outcomes. SNP-level associations included three SNPs with MI (one LDLR, two LIPC) and two SNPs with stroke (one CETP, one LDLR). The number of observed SNP associations was no greater than expected by chance. CONCLUSION:Several potential novel associations or interactions of SNPs in ABCB1, CETP, LDLR, and LIPC with MI and stroke were identified; however, our results should be regarded as hypothesis generating until corroborated by other studies.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Hindorff LA,Lemaitre RN,Smith NL,Bis JC,Marciante KD,Rice KM,Lumley T,Enquobahrie DA,Li G,Heckbert SR,Psaty BMdoi
10.1097/FPC.0b013e3283033528subject
Has Abstractpub_date
2008-08-01 00:00:00pages
677-82issue
8eissn
1744-6872issn
1744-6880pii
01213011-200808000-00004journal_volume
18pub_type
杂志文章abstract:OBJECTIVES:Prolonged activation of the β-1 adrenergic receptor (ADRB1) is associated with receptor desensitization. This process has been suggested to have important pathophysiological and clinical implications in conditions such as congestive heart failure. The contribution of genetic factors to this process is a subj...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000338
更新日期:2018-06-01 00:00:00
abstract:OBJECTIVE:Glutathione S-transferase enzymes (GSTs; EC: 2.5.1.18) constitute the principal phase II superfamily, which plays a key role in cellular detoxification. GST genes are organized in chromosomal clusters; most of these genes are polymorphic, mainly due to single nucleotide substitutions. Different studies proved...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328349da4d
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment. METHODS:A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a phenytoin prescriptio...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000383
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND/AIM:MicroRNAs (miRNAs) are small noncoding RNAs that have been implicated in mechanisms underlying various types of cancers including hepatocellular carcinoma (HCC). Reports have indicated that single nucleotide polymorphisms in miRNA-196A2 and miRNA-146A genes may contribute to the risk of progression of he...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000187
更新日期:2016-02-01 00:00:00
abstract::The genetically polymorphic cytochrome P450 2C9 (CYP2C9) metabolizes many important drugs. Among them, phenytoin has been used as a probe to determine CYP2C9 phenotype by measuring the urinary excretion of its major metabolite, S-enantiomer of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Phenytoin pharmacokinetic i...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000174787.92861.91
更新日期:2005-11-01 00:00:00
abstract:OBJECTIVES:The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine. METHODS:A subset of HIV-positive individuals receiving...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000417
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:Irreversible hearing loss is a frequent side effect of the chemotherapeutic agent cisplatin and shows considerable interpatient variability. The variant rs1872328 in the ACYP2 gene was recently identified as a risk factor for the development of cisplatin-induced ototoxicity in children with brain tumors. We a...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000212
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVE:Identification of biomarkers that could predict gemcitabine efficacy and toxicity is a key issue in the development of individualized therapy. The aim of our study was to evaluate the influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma (MM). METHODS:In ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834e3572
更新日期:2012-01-01 00:00:00
abstract::Recent investigations suggest genetic susceptibility of allopurinol-induced severe cutaneous adverse reactions (SCARs). However, the strength of association was variable according to phenotypes and ethnic backgrounds. To explore genetic markers for allopurinol-induced SCARs in Koreans, we genotyped human leukocyte ant...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834282b8
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:GW320659, a highly selective neuronal norepinephrine and dopamine re-uptake inhibitor, has been evaluated for the treatment of obesity. Scrutiny of the weight loss data from a phase II study (GlaxoSmithKline study OBS20001) showed a wide variation in weight loss response following GW320659 treatment and the ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/01213011-200512000-00006
更新日期:2005-12-01 00:00:00
abstract::The existence of genetic polymorphisms in metabolizing enzymes can be regarded as one of the principal causes of interindividual variation in response to drugs and adverse reactions. In the case of enzyme CYP2C9, the presence of genetic coding variants could be considered a risk factor for suffering from gastrointesti...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,评审
doi:10.1097/FPC.0b013e328346d2bb
更新日期:2011-07-01 00:00:00
abstract:OBJECTIVES:Among serotonin (5-HT) receptors, the 5-HT3 receptor is the only ligand-gated ion channel. 5-HT3 antagonists such as ondansetron and tropisetron may improve auditory gating and neurocognitive deficits in schizophrenic patients. Moreover, many antipsychotic drugs are antagonists at 5-HT3 receptors. However, t...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,随机对照试验
doi:10.1097/FPC.0b013e3283313296
更新日期:2009-11-01 00:00:00
abstract:OBJECTIVES:A total of 2402 patients with arsenic-related skin lesions, such as hyperkeratosis, hyperpigmentation or hypopigmentation, or even skin cancer in a few villages in Southwest Guizhou Autonomous Prefecture, China represent a unique case of endemic arsenism related with indoor combustion of high arsenic coal. T...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000230415.82349.4b
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:For prevention of joint destruction in rheumatoid arthritis, optimal management of therapy with disease-modifying antirheumatic drugs is essential. Pharmacogenomic evidence, if reliable, may be incorporated in the treatment of rheumatoid arthritis to achieve a more efficient activity control with minimized a...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000236326.80809.b1
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:Paraoxonase-1 (PON1) is synthesized in the liver and is bound to high-density lipoprotein particles in blood. PON1 protects against the development of atherosclerosis by metabolizing proatherogenic-oxidized lipids. The Southeastern USA (excluding Florida) has the country's highest age-adjusted mortality rate ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834cebc6
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVE:Vitamin K is an essential cofactor for the synthesis of several blood coagulation factors. It has been suggested that the apolipoprotein E (ApoE) genotype has profound effects on vitamin K status. Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of c...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01213011-200502000-00002
更新日期:2005-02-01 00:00:00
abstract::The study aimed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome in advanced colorectal cancer (CRC) patients treated with single-agent Cetuximab. Polymorphisms of interest in the EGFR pathway include: cyclin D1 (CCND1) A870G, cyclooxygenase 2 (Cox-2) G-7...
journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/01.fpc.0000220562.67595.a5
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:The immunosuppressive drug tacrolimus requires strict therapeutic monitoring due to its narrow therapeutic index and great inter-individual variability. Cytochrome P450 3A4 (Cyp3A4) and Cyp3A5 are the most important contributors to tacrolimus metabolism while the P-glycoprotein pump (MDR-1) modulates its bioa...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000220571.20961.dd
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVES:This study investigated the involvement of ADH4 gene polymorphisms in the susceptibility to alcohol use disorders. METHODS:Thirty-eight single-nucleotide polymorphisms (SNPs) in and around the ADH4 gene were investigated in 136 Italian alcoholics and 276 healthy controls. A new approach based on a bioinform...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32834d05c8
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVES:This study aimed to explore the influence of variation in DRD2, DRD3, CYP2D6, CYP3A4, and CYP3A5 genes on treatment resistance to typical neuroleptics in a Brazilian sample of patients with schizophrenia. METHODS:One polymorphism at DRD2 gene, five at DRD3, 24 at CYP2D6, nine at CYP3A4 gene, and one at CYP3...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328301a763
更新日期:2008-07-01 00:00:00
abstract::Two recent screens for copy-number variations in the entire human genome found 12.4 gene copy number variations per person, including 2.5% of individuals with gains between 7q21.1 and 7q22.1, the chromosomal location of CYP3A4. CYP3A4 is involved in the metabolism of approximately 50% of all drugs, including many canc...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000194421.35641.70
更新日期:2006-06-01 00:00:00
abstract:OBJECTIVE:To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32835aa888
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVE:To investigate the utility of statistical tools in translating Affymetrix Drug Metabolizing Enzyme and Transporter (DMET) Assay single-nucleotide polymorphisms (SNPs) into common consensus star alleles. METHODS:DMET SNP data from clinical trials in different ethnicities were pooled for analyses. Three differ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000047
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVES:Epidemiological studies documented associations between single nucleotide polymorphisms (SNPs) in the nucleotide excision repair gene XPD/ERCC2 and cancer risk. Little is known, however, about the underlying mechanisms for these associations. We explored a novel mechanism that could further explain the repor...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3280115e63
更新日期:2007-11-01 00:00:00
abstract::Fumaric acid esters (FAE) are beneficial in the treatment of psoriasis. However, about a third of psoriasis patients do not respond to FAE. We aimed to determine whether glutathione-S-transferase (GST) M1 and GSTP1 polymorphisms are associated with treatment outcome in psoriasis patients treated with FAE. We studied 8...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000218
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVE:Individual differences in drug efficacy and toxicity remain an important clinical concern. We investigated copy number variation (CNV) frequencies for pharmacogenes using The Cancer Genome Atlas dataset. MATERIALS AND METHODS:One hundred and fifty-two pharmacogenes were selected from liver hepatocellular car...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000097
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVES:The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment decisions. Therefore, our objective is to present the methods and feasibility of a pilot pharmacogenomic study set in the ED that measured pe...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000414
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:The mammalian target of rapamycin (m-TOR) inhibitor sirolimus is an immunosuppressive drug used in kidney transplantation. m-TOR binds with Raptor and phosphorylates p70S6 kinase, a protein involved in numerous cell signalling pathways. We examined the association of candidate polymorphisms in m-TOR, Raptor ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FPC.0b013e328357359d
更新日期:2012-10-01 00:00:00
abstract::We recently showed an association between the FCGR3A V/F polymorphism and the biological response [assessed on the basis of a C-reactive protein (CRP) concentration decrease] to infliximab in Crohn's disease. The CRP and FCGR3A genes are located on the same 1q23 locus. The present study aimed: (i) to exclude a linkage...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000182776.57437.d8
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:Alcohol is detoxified in the liver by oxidizing enzymes that require nicotinamide adenine dinucleotide (NAD+) such that, in the rat, the availability of NAD+ contributes to control voluntary ethanol intake. The UChA and UChB lines of Wistar rats drink low and high amounts of ethanol respectively and differ in...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32832dc12a
更新日期:2009-07-01 00:00:00