Pharmacogenomic incidental findings in 308 families: The NIH Undiagnosed Diseases Program experience.

Genet Med. 2016 Jun 2;

Authors: Lee EM, Xu K, Mosbrook E, Links A, Guzman J, Adams DR, Flynn E, Valkanas E, Toro C, Tifft CJ, Boerkoel CF, Gahl WA, Sincan M

Abstract
PURPOSE: Using single-nucleotide polymorphism (SNP) chip and exome sequence data from individuals participating in the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP), we evaluated the number and therapeutic informativeness of incidental pharmacogenetic variants.
METHODS: Pharmacogenomics Knowledgebase (PharmGKB) annotated sequence variants were identified in 1,101 individuals. Medication records of participants were used to identify individuals prescribed medications with a genetic variant that might alter efficacy.
RESULTS: A total of 395 sequence variants, including 19 PharmGKB 1A and 1B variants, were identified in SNP chip sequence data, and 388 variants, including 21 PharmGKB 1A and 1B variants, were identified in the exome sequence data. Nine participants had incidental pharmacogenetic variants associated with altered efficacy of a prescribed medication.
CONCLUSIONS: Despite the small size of the NIH UDP patient cohort, we identified pharmacogenetic incidental findings potentially useful for guiding therapy. Consequently, groups conducting clinical genomic studies might consider reporting of pharmacogenetic incidental findings.Genet Med advance online publication 02 June 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.47.

PMID: 27253732 [PubMed - as supplied by publisher]

Pharmacogenomics of preterm birth prevention and treatment.

BJOG. 2016 Feb;123(3):368-75

Authors: Manuck TA

Abstract
UNLABELLED: Pharmacogenomics and personalised medicine incorporate genetic factors, historical data, and environmental exposures to predict individual variation in response to medications. The study of pharmacology and pharmacogenomics is challenging in obstetrics, and our knowledge in this area lags behind other disciplines of medicine. Some preliminary data, however, suggest that some of the interindividual variation seen in response to medications given for the prevention (progesterone) and the treatment (nifedipine, terbutaline, and others) of preterm labour may be caused by pharmacogenomic effects. A comprehensive approach, integrating clinical data, environmental factors, including concomitant medications and genotype, to optimise the prevention and treatment strategies for preterm birth, is urgently needed.
TWEETABLE ABSTRACT: Some of the variation to meds for prematurity prevention/treatment may arise from pharmacogenomic effects.

PMID: 26542879 [PubMed - indexed for MEDLINE]

Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics in the Era of Targeted Therapies.

Am Soc Clin Oncol Educ Book. 2016;35:e175-e184

Authors: Calvo E, Walko C, Dees EC, Valenzuela B

Abstract
The complex nature of the pharmacologic aspects of cancer therapeutics has become more apparent in the past several years with the arrival of a cascade of target-based agents and the difficult challenge of bringing individualized precision medicine to oncology. Interpatient variability in drug action, singularly in novel agents, is in part caused by pharmacogenomic (PG), pharmacokinetic, and pharmacodynamic (PD) factors, and drug selection and dosing should take this into consideration to optimize the benefit for our patients in terms of antitumor activity and treatment tolerance. In this regard, somatic genetic evaluation of tumors is useful in not only predicting response to initial targeted therapies but also in anticipating and guiding therapy after the development of acquired resistance; therapeutic drug monitoring of novel small molecules and monoclonal antibodies must be incorporated in our day-to-day practice to minimize the negative effect on clinical outcome of interindividual variability on pharmacokinetic processes of these drugs for all patients, but especially for fragile patient populations and those with organ dysfunction or comorbidities. For these populations, incorporating frailty assessment tools into trials of newer agents and validating frailty-based dose adjustment should be an important part of further drug development.

PMID: 27249721 [PubMed - as supplied by publisher]

Evidence for extensive pleiotropy among pharmacogenes.

Pharmacogenomics. 2016 Jun 1;:0

Authors: Oetjens MT, Bush WS, Denny JC, Birdwell K, Kodaman N, Verma A, Dilks HH, Pendergrass SA, Ritchie MD, Crawford DC

Abstract
AIM: We sought to identify potential pleiotropy involving pharmacogenes.
METHODS: We tested 184 functional variants in 34 pharmacogenes for associations using a custom grouping of International Classification and Disease, Ninth Revision billing codes extracted from deidentified electronic health records of 6892 patients.
RESULTS: We replicated several associations including ABCG2 (rs2231142) and gout (p = 1.73 × 10(-7); odds ratio [OR]: 1.73; 95% CI: 1.40-2.12); and SLCO1B1 (rs4149056) and jaundice (p = 2.50 × 10(-4); OR: 1.67; 95% CI: 1.27-2.20).
CONCLUSION: In this systematic screen for phenotypic associations with functional variants, several novel genotype-phenotype combinations also achieved phenome-wide significance, including SLC15A2 rs1143672 and renal osteodystrophy (p = 2.67 × 10(-) (6); OR: 0.61; 95% CI: 0.49-0.75).

PMID: 27249515 [PubMed - as supplied by publisher]

Requirements for comprehensive pharmacogenetic genotyping platforms.

Pharmacogenomics. 2016 Jun 1;:0

Authors: Lauschke VM, Ingelman-Sundberg M

Abstract
Recent research highlighted the large extent of rare variants in pharmacogenes and, on this basis, it was estimated that rare variants account for 30-40% of the functional variability in pharmacogenes. It has been proposed that comprehensive next-generation sequencing (NGS)-based sequencing of pharmacogenes could soon be a cost-effective methodology for clinical routine genotyping. Yet, multiple challenges on technical, interpretative and ethical levels need to be overcome to enable the reasonable dissemination of comprehensive pharmacogenetic genotyping, that includes rare genetic variation, into clinical practice. We argue that current pre-emptive pharmacogenetic testing cannot be based on comprehensive approaches but needs to be restricted to validated variants. Rather, comprehensive strategies should only be used for retrospective analyses of patients exhibiting unanticipated drug responses. Thereby, subsequent to computational analyses and functional validations, emerging variants with confirmed functional relevance can be incorporated into candidate genotyping strategies, thus refining and enhancing future pre-emptive genetic testing.

PMID: 27248710 [PubMed - as supplied by publisher]

Identifying genetic loci affecting antidepressant drug response in depression using drug-gene interaction models.

Pharmacogenomics. 2016 Jun 1;

Authors: Noordam R, Avery CL, Visser LE, Stricker BH

Abstract
Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., 'treated-only design', statistical power) and we will discuss how specifically drug-gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression.

PMID: 27248517 [PubMed - as supplied by publisher]

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis.

Oncotarget. 2016 May 29;

Authors: Chen J, Wang Z, Zou T, Cui J, Yin J, Zheng W, Jiang W, Zhou H, Liu Z

Abstract
Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/ C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients.

PMID: 27248474 [PubMed - as supplied by publisher]

Pharmacogenetics of ribavirin-induced anemia in HCV patients.

Pharmacogenomics. 2016 Jun 1;

Authors: D'Avolio A, Cusato J, De Nicolò A, Allegra S, Di Perri G

Abstract
Dual therapy (pegylated interferon plus ribavirin) was considered the standard of care for hepatitis C virus (HCV) treatment until 2011, when the first-wave direct-acting antivirals were added to this regimen for HCV genotype-1 patients to increase the sustained virological response rate. The second-wave direct-acting antivirals entered the clinical use also in some ribavirin (RBV)- and/or interferon-free combinations. Nevertheless, since some of the new therapeutic regimens also include RBV and its use results still associated with hemolytic anemia, this requires countermeasures to be prevented. These include the identification of several host predictive factors involved in RBV absorption, distribution, metabolism, elimination and many others that might influence this toxic effect. For this reason, we provided an overview of the potential role of pharmacogenomics in predisposing RBV-treated HCV patients to anemia.

PMID: 27248282 [PubMed - as supplied by publisher]

Evaluation of methodology for the analysis of 'time-to-event' data in pharmacogenomic genome-wide association studies.

Pharmacogenomics. 2016 Jun 1;:0

Authors: Syed H, Jorgensen AL, Morris AP

Abstract
AIM: To evaluate the power to detect associations between single nucleotide polymorphisms and time-to-event outcomes across a range of pharmacogenomic study designs while comparing alternative regression approaches.
MATERIALS & METHODS: Simulations were conducted to compare Cox proportional hazards modeling accounting for censoring and logistic regression modeling of a dichotomized outcome at the end of the study.
RESULTS: The Cox proportional hazards model was demonstrated to be more powerful than the logistic regression analysis. The difference in power between the approaches was highly dependent on the rate of censoring.
CONCLUSION: Initial evaluation of single nucleotide polymorphism association signals using computationally efficient software with dichotomized outcomes provides an effective screening tool for some design scenarios, and thus has important implications for the development of analytical protocols in pharmacogenomic studies.

PMID: 27248145 [PubMed - as supplied by publisher]

Pharmacogenomics of long-acting β2-agonists.

Expert Opin Drug Metab Toxicol. 2015;11(11):1733-51

Authors: Blake K, Lima J

Abstract
INTRODUCTION: Long-acting β2-agonists are an effective class of drugs, when combined with inhaled corticosteroids, for reducing symptoms and exacerbations in patients with asthma that is not adequately controlled by inhaled corticosteroids alone. However, because this class of drugs has been associated with severe adverse events, including hospitalization and death in small numbers of patients, efforts to identify a pharmacogenetic profile for patients at risk has been diligently investigated.
AREAS COVERED: The PubMed search engine of the National Library of Medicine was used to identify English-language and non-English language articles published from 1947 to March 2015 pertinent to asthma, pharmacogenomics, and long-acting β2-agonists. Keywords and topics included: asthma, asthma control, long-acting β2-agonists, salmeterol, formoterol, pharmacogenetics, and pharmacogenomics. This strategy was also used for the Cochrane Library Database and CINAHL. Reference types were randomized controlled trials, reviews, and editorials. Additional publications were culled from reference lists. The publications were reviewed by the authors and those most relevant were used to support the topics covered in this review.
EXPERT OPINION: Children, who carry the ADRB2 Arg16Arg genotype, may be at greater risk than adults for severe adverse events. Rare ADRB2 variants appear to provide better clues for identifying the at-risk population of asthmatics.

PMID: 26235677 [PubMed - indexed for MEDLINE]

The pharmacogenomics of osteosarcoma.

Pharmacogenomics J. 2016 May 31;

Authors: Serra M, Hattinger CM

Abstract
Osteosarcoma (OS), the most common malignant tumor of bone, is presently treated with multidrug neoadjuvant chemotherapy protocols, which allow to cure 60-65% of patients but also induce toxicity events that cannot be predicted or efficiently prevented. The identification and validation of pharmacogenomic biomarkers is, therefore, absolutely warranted to provide the bases for planning personalized treatments with the aim to increase the therapeutic benefits and to avoid or limit unnecessary toxicities. As several targeted therapies against molecular and immunological markers in OS are presently under clinical investigation, it may be speculated that some new agents for innovative treatments may emerge in the next years. However, the real improvement of therapeutic perspectives for OS is strictly connected to the identification of pharmacogenomic biomarkers that may stratify patients in responders or non-responders and identify those individuals with higher susceptibility to treatment-associated toxicity. This review provides an overview of the pharmacogenomic biomarkers identified so far in OS, which appear to be promising candidates for a translation to clinical practice, after further investigation and/or prospective validation.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.45.

PMID: 27241064 [PubMed - as supplied by publisher]

Influence of ABCB1 and ABCG2 polymorphisms on the antiemetic efficacy in patients with cancer receiving cisplatin-based chemotherapy: a TRIPLE pharmacogenomics study.

Pharmacogenomics J. 2016 May 31;

Authors: Tsuji D, Yokoi M, Suzuki K, Daimon T, Nakao M, Ayuhara H, Kogure Y, Shibata K, Hayashi T, Hirai K, Inoue K, Hama T, Takeda K, Nishio M, Itoh K

Abstract
Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.38.

PMID: 27241063 [PubMed - as supplied by publisher]

Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer.

Pharmacogenomics J. 2016 May 31;

Authors: Sunakawa Y, Cao S, Volz NB, Berger MD, Yang D, Parekh A, Zhang W, Matsusaka S, Ning Y, Stremitzer S, Stintzing S, Sebio A, Okazaki S, Wakatsuki T, Azuma M, Watanabe M, Koizumi W, Wu AH, Lenz HJ

Abstract
Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P=0.015, P=0.043, respectively). In US cohort the C allele predicted worse OS (P=0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.46.

PMID: 27241062 [PubMed - as supplied by publisher]

Comparing cytochrome P450 pharmacogenetic information available on United States drug labels and European Union Summaries of Product Characteristics.

Pharmacogenomics J. 2016 May 31;

Authors: Reis-Pardal J, Rodrigues A, Rodrigues E, Fernandez-Llimos F

Abstract
Regulatory agencies are increasing the pharmacogenomic information in their official drug labeling. However, despite the importance of regulatory harmonization, this implementation may not be running in parallel among major agencies. Comparing labeling of medicines approved by different agencies may identify gaps to solve. Our study compared the cytochrome P450 pharmacogenetic information included in the United States (US) Food and Drug Administration (FDA) drug labels and European Union (EU) Summaries of Product Characteristics (SmPCs). US labels presented significantly more specific pharmacogenetic subheadings (51 vs 26%), more prevalence and pharmacokinetic data for each metabolic phenotype (59 vs 25% and 82 vs 48%, respectively) and more applicable information about dose modifications required (25 vs 5%). Approximately 75% of the US labels evaluated scored higher on the overall quality than the analogous EU SmPCs, and this difference was not associated with the time since the EU SmPCs' last review. To enhance harmonization, regulatory agencies should simultaneously introduce the pharmacogenetic information in their drug labeling.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.40.

PMID: 27241061 [PubMed - as supplied by publisher]

HLA-B18 as a risk factor of short-term progression to severe liver fibrosis in HIV/HCV co-infected patients with absent or minimal fibrosis: implications for timing of therapy.

Pharmacogenomics J. 2016 May 31;

Authors: Frías M, Rodríguez-Cano D, Cuenca-López F, Macías J, Gordon A, Manzanares-Martín B, Pineda JA, Camacho Á, Torre-Cisneros J, Peña J, Rivero-Juárez A, Rivero A

Abstract
Our aim was to analyze the influence of HLA-B haplotypes on liver fibrosis progression in HIV/hepatitis C virus (HCV) co-infected patients. Retrospective longitudinal study including HIV/HCV, non-cirrhotic and HCV treatment-naïve patients. The main outcome variable was liver fibrosis progression of at least one stage. One hundred and four patients constituted the study population (F0-F1: 62 (59.6%); F2: 22 (21.2%); F3: 20 (19.2%)). During a median follow-up of 54.5 months (IQR: 26.2-77), 45 patients (43.3%) showed an increase in the stage of liver fibrosis (time to event: 29 (IQR: 14-49.5) months). HLA-B18(pos) patients more frequently had a higher and faster fibrosis progression rate (73.3%; 24 (IQR: 8-29) months) than HLA-B18(neg) patients (38.2%; 34.5 (IQR: 14.7-51.2) months). This association was also observed in the development of F3-F4 fibrosis among F0-F2 patients (HLA-B18(pos): 69.2%; 18 (6.5-37) months vs HLA-B18(neg): 28.2%; 37 (IQR: 19-52) months). These results could impact the timing of HCV therapy in F0-F2 patients.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.42.

PMID: 27241060 [PubMed - as supplied by publisher]

Genetic epidemiology of pharmacogenetic variants in South East Asian Malays using whole-genome sequences.

Pharmacogenomics J. 2016 May 31;

Authors: Sivadas A, Salleh MZ, Teh LK, Scaria V

Abstract
Expanding the scope of pharmacogenomic research by including multiple global populations is integral to building robust evidence for its clinical translation. Deep whole-genome sequencing of diverse ethnic populations provides a unique opportunity to study rare and common pharmacogenomic markers that often vary in frequency across populations. In this study, we aim to build a diverse map of pharmacogenetic variants in South East Asian (SEA) Malay population using deep whole-genome sequences of 100 healthy SEA Malay individuals. We investigated the allelic diversity of potentially deleterious pharmacogenomic variants in SEA Malay population. Our analysis revealed 227 common and 466 rare potentially functional single nucleotide variants (SNVs) in 437 pharmacogenomic genes involved in drug metabolism, transport and target genes, including 74 novel variants. This study has created one of the most comprehensive maps of pharmacogenetic markers in any population from whole genomes and will hugely benefit pharmacogenomic investigations and drug dosage recommendations in SEA Malays.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.39.

PMID: 27241059 [PubMed - as supplied by publisher]

COMT val158met moderation of dopaminergic drug effects on cognitive function: a critical review.

Pharmacogenomics J. 2016 May 31;

Authors: Schacht JP

Abstract
The relationship between dopamine (DA) tone in the prefrontal cortex (PFC) and PFC-dependent cognitive functions (for example, working memory, selective attention, executive function) may be described by an inverted-U-shaped function, in which both excessively high and low DA is associated with impairment. In the PFC, the COMT val158met single nucleotide polymorphism (rs4680) confers differences in catechol-O-methyltransferase (COMT) efficacy and DA tone, and individuals homozygous for the val allele display significantly reduced cortical DA. Many studies have investigated whether val158met genotype moderates the effects of dopaminergic drugs on PFC-dependent cognitive functions. A review of 25 such studies suggests evidence for this pharmacogenetic effect is mixed for stimulants and COMT inhibitors, which have greater effects on D1 receptors, and strong for antipsychotics, which have greater effects on D2 receptors. Overall, COMT val158met genotype represents an enticing target for identifying individuals who are more likely to respond positively to dopaminergic drugs.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.43.

PMID: 27241058 [PubMed - as supplied by publisher]

Anti-tumor necrosis factor-α therapy in uveitis.

Surv Ophthalmol. 2015 Nov-Dec;60(6):575-89

Authors: Cordero-Coma M, Sobrin L

Abstract
Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy.

PMID: 26164735 [PubMed - indexed for MEDLINE]

SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study.

BMC Cancer. 2016;16(1):337

Authors: Reimer T, Kempert S, Gerber B, Thiesen HJ, Hartmann S, Koczan D

Abstract
BACKGROUND: Because inheritance is recognized as playing a role in age at menarche and natural menopause, the development of chemotherapy-induced amenorrhea (CIA) might depend on inherited genetic factors; however, studies that explore such a correlation are few and have received scant attention. Given the importance of this topic we conducted a comprehensive genotype study in young women (≤45 years) with early-stage breast cancer.
METHODS: Our approach tested the effect of variant polymorphisms in drug metabolism enzymes (DMEs) using a predesigned pharmacogenomics panel (TaqMan® OpenArray®, Life Technologies GmbH, Darmstadt, Germany) in premenopausal women (n = 50). Patients received contemporary chemotherapy; in all cases a cyclophosphamide-based regimen with a dose of at least 500 mg/m(2) for six cycles. CIA was considered to be present in women with no resumption of menstrual bleeding within 12 months after completion of chemotherapy or goserelin.
RESULTS: Twenty-six patients (52 %) showed CIA during follow-up whereas 24 women (48 %) remained premenopausal. Of all the DMEs studied, only the SLCO1B1*5 (rs4149056) genotype was associated with the development of CIA (P = 0.017). Of the 26 patients who were homozygous for the T/T allele SLCO1B1*5, 18 (69.2 %) developed CIA compared with 8 (30.8 %) of the 22 patients who were heterozygous (C/T allele). The association of heterozygous SLCO1B1*5 allele (OR 0.038; 95%CI: 0.05-0.92) with a lower risk of developing CIA remained significant in a binary logistic regression analysis that include age, SLCO1B1*5 allele variants, and goserelin therapy.
CONCLUSIONS: Patient age and SLCO1B1*5 allele variants predict the likelihood of young women with breast cancer developing CIA.

PMID: 27234217 [PubMed - as supplied by publisher]

Genetic polymorphisms of pharmacogenomic VIP variants in the Mongol of Northwestern China.

BMC Genet. 2016;17(1):70

Authors: Jin T, Shi X, Wang L, Wang H, Feng T, Kang L

Abstract
BACKGROUND: Within a population, the differences of pharmacogenomic variant frequencies may produce diversities in drug efficacy, safety, and the risk associated with adverse drug reactions. With the development of pharmacogenomics, widespread genetic research on drug metabolism has been conducted on major populations, but less is known about minorities.
RESULTS: In this study, we recruited 100 unrelated, healthy Mongol adults from Xinjiang and genotyped 85 VIP variants from the PharmGKB database. We compared our data with eleven populations listed in 1000 genomes project and HapMap database. We used χ(2) tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations.
CONCLUSIONS: Our results demonstrated that different polymorphic allele frequencies exist between different nationalities,and indicated Mongol is most similar to Chinese populations, followed by JPT. This information on the Mongol population complements the existing pharmacogenomic data and provides a theoretical basis for screening and therapy in the different ethnic groups within Xinjiang.

PMID: 27233804 [PubMed - as supplied by publisher]