11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/10/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Impact of Gastric H(+)/K(+)-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects.

Front Pharmacol. 2017;8:670

Authors: Sun LN, Cao Y, Li YQ, Fang YQ, Zhang HW, Wang MF, Xie LJ, Chen J, Yang ZC, Bian ML, Li H, Zhang PP, Wei JF, Meng L, Zhang XH, Zhao P, Wang YQ

Abstract
Background: Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric H(+)/K(+)-ATPase, CYP2C19, and ABCB1 polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects. Methods: A total of 51 subjects were enrolled for pharmacokinetic and pharmacodynamic study after a single intravenous administration of 20 or 30 mg dexlansoprazole. Plasma concentrations were determined using a chiral liquid chromatography-mass spectrometry method. The intragastric pH and baseline-adjusted intragastric pH parameters were introduced to evaluate the pharmacodynamic characters. Genotyping was performed by polymerase chain reaction. Results: The pharmacokinetic parameters were significantly influenced by CYP2C19 phenotypes, and gastric acid secretion inhibition were affected by both gastric H(+)/K(+)-ATPase and CYP2C19 polymorphisms. Gastric H(+)/K(+)-ATPase genotypes had greater effects than CYP2C19 genotypes on the suppression of gastric acid secretion. Conclusion: Gastric H(+)/K(+)-ATPase polymorphism may be one of the main reasons that cause insufficient gastric acid inhibition.

PMID: 29018343 [PubMed]

A common missense variant of LILRB5 is associated with statin intolerance and myalgia.

Eur Heart J. 2017 Aug 29;:

Authors: K Siddiqui M, Maroteau C, Veluchamy A, Tornio A, Tavendale R, Carr F, Abelega NU, Carr D, Bloch K, Hallberg P, Yue QY, Pearson ER, Colhoun HM, Morris AD, Dow E, George J, Pirmohamed M, Ridker PM, Doney ASF, Alfirevic A, Wadelius M, Maitland-van der Zee AH, Chasman DI, Palmer CNA, PREDICTION-ADR Consortium

Abstract
Aims: A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study.
Methods and results: In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34-2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07-1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05-2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10-1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16-1.54).
Conclusion: This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.

PMID: 29020356 [PubMed - as supplied by publisher]

N-acetyltransferase 2 Genotype-dependent N-acetylation of Hydralazine in Human Hepatocytes.

Drug Metab Dispos. 2017 Oct 10;:

Authors: Allen CE, Doll MA, Hein DW

Abstract
Hydralazine is used in treatment of essential hypertension and is under investigation for epigenetic therapy in the treatment of neoplastic and renal diseases. N-acetyltransferase 2 (NAT2) exhibits a common genetic polymorphism in human populations. Following recombinant expression in yeast, human NAT2 exhibited an apparent Km (20.1 ± 8.8 μM) for hydralazine over 20-fold lower than the apparent Km (456 ± 57 μM) for recombinant human NAT1 (p=0.0016). The apparent Vmax for recombinant human NAT1 (72.2 ± 17.9 nmoles acetylated/min/mg protein) was significantly (p=0.0245) lower than recombinant human NAT2 (153 ± 15 nmoles acetylated/min/mg protein) reflecting 50-fold higher clearance for recombinant human NAT2. Hydralazine N-acetyltransferase activities exhibited a robust acetylator gene dose-response in cryopreserved human hepatocytes both in vitro and in situ. Hydralazine N-acetyltransferase activities in vitro differed significantly with respect to NAT2 genotype at 1000 μM (p=0.0319); 100 μM (p=0.002); and 10 μ;M hydralazine (p=0.0029). Hydralazine N-acetyltransferase activities differed significantly (p<0.001) among slow acetylator hepatocytes, (NAT2*5B/*5B > NAT2*5B/*6A > NAT2*6A/*6A). The in situ hydralazine N-acetylation rates differed significantly with respect to NAT2 genotype following incubation with 10 μM (p=0.002) or 100 μM (p=0.0015) hydralazine and were higher following incubation with 100 μM (10-fold) than 10 μM (4.5-fold) hydralazine. Our results clearly document NAT2 genotype-dependent N-acetylation of hydralazine in human hepatocytes, suggesting that hydralazine efficacy and safety could be improved by NAT2 genotype-dependent dosing strategies.

PMID: 29018032 [PubMed - as supplied by publisher]

Author's Reply: Comments on "Vitamin Pharmacogenomics: New Insight into Individual Differences in Diseases and Drug Responses".

Genomics Proteomics Bioinformatics. 2017 Oct 07;:

Authors: Zhang W

PMID: 29017968 [PubMed - as supplied by publisher]

Comments on "Vitamin Pharmacogenomics: New Insight into Individual Differences in Diseases and Drug Responses".

Genomics Proteomics Bioinformatics. 2017 Oct 07;:

Authors: Greenfield T

PMID: 29017966 [PubMed - as supplied by publisher]

HLA-associated drug hypersensitivity and the prediction of adverse drug reactions.

Pharmacogenomics. 2017 Oct 11;:

Authors: Negrini S, Becquemont L

Abstract
Adverse drug reactions are an important cause of morbidity and mortality and constitute the leading reason of drug withdrawal from the market. Besides classical reactions that are related to pharmacologic activity of the drug, some reactions are unpredictable, not dose dependent, and seem to occur in genetically predisposed individuals. The majority of this reaction is immunologically driven and they are referred to as hypersensitivity reactions. A growing number of studies provided evidences that specific HLA alleles increase the risk of developing hypersensitivity drug reactions. In this context, drug hypersensitivities that have more robust pharmacogenetic data include abacavir hypersensitivity syndrome and severe cutaneous adverse reactions induced by allopurinol and carbamazepine.

PMID: 29017379 [PubMed - as supplied by publisher]

Influence of common polymorphisms in the SLC5A2 gene on metabolic traits in subjects at increased risk of diabetes and on response to empagliflozin treatment in patients with diabetes.

Pharmacogenet Genomics. 2017 Apr;27(4):135-142

Authors: Zimdahl H, Haupt A, Brendel M, Bour L, Machicao F, Salsali A, Broedl UC, Woerle HJ, Häring HU, Staiger H

Abstract
OBJECTIVE: Inhibition of the renal sodium-glucose cotransporter 2 (SGLT2) is a novel concept in the therapy of diabetes mellitus. In this study, we first assessed whether common single nucleotide polymorphisms (SNPs) in the SGLT2-encoding gene SLC5A2 affect diabetes-related metabolic traits in subjects at risk for type 2 diabetes and, second, whether these have pharmacogenetic relevance by interfering with the response to empagliflozin treatment in patients with type 2 diabetes.
PATIENTS AND METHODS: Samples from a metabolically well-phenotyped cross-sectional study population (total N=2600) at increased risk for type 2 diabetes and pooled pharmacogenetic samples from patients from four phase III trials of empagliflozin (in total: 603 receiving empagliflozin, 305 receiving placebo) were genotyped for five common SNPs (minor allele frequencies ≥5%) present in the SLC5A2 gene locus.
RESULTS: In the cross-sectional study, none of the SLC5A2 SNPs significantly influenced metabolic traits such as body fat, insulin sensitivity/resistance, insulin release, HbA1c, plasma glucose, or systolic blood pressure when multiple testing was taken into account (all P≥0.0083). Further, no relevant effect on response to treatment with empagliflozin on HbA1c, fasting glucose, weight, or systolic blood pressure was observed for the SNPs tested in the pharmacogenetic study.
CONCLUSION: Common genetic variants in the SLC5A2 gene neither affects diabetes-related metabolic traits nor have a clinically relevant impact on response to treatment with the SGLT2 inhibitor empagliflozin.

PMID: 28134748 [PubMed - indexed for MEDLINE]

Activation of Liver X Receptor Attenuates Oleic Acid-Induced Acute Respiratory Distress Syndrome.

Am J Pathol. 2016 Oct;186(10):2614-22

Authors: Zhao Z, Xu D, Li S, He B, Huang Y, Xu M, Ren S, Li S, Wang H, Xie W

Abstract
Liver X receptors (LXRs) were identified as receptors that sense oxidized cholesterol derivatives. LXRs are best known for their hepatic functions in regulating cholesterol metabolism and triglyceride synthesis, but whether and how LXRs play a role in the lung diseases is less understood. To study the function of LXRs in acute respiratory distress syndrome (ARDS), we applied the oleic acid (OA) model of ARDS to mice whose LXR was genetically or pharmacologically activated. The VP-LXRα knock-in (LXR-KI) mice, in which a constitutively activated LXRα (VP-LXRα) was inserted into the mouse LXRα locus, were used as the genetic gain-of-function model. We showed that the OA-induced lung damages, including the cytokine levels and total cell numbers and neutrophil numbers in the bronchoalveolar lavage fluid, the wet/dry weight ratio, and morphological abnormalities were reduced in the LXR-KI mice and wild-type mice treated with the LXR agonist GW3965. The pulmonoprotective effect of GW3965 was abolished in the LXR-null mice. Consistent with the pulmonoprotective effect of LXR and the induction of antioxidant enzymes by LXR, the OA-induced suppression of superoxide dismutase and catalase was attenuated in LXR-KI mice and GW3965-treated wild-type mice. Taken together, our results demonstrate that activation of LXRs can alleviate OA-induced ARDS by attenuating the inflammatory response and enhancing antioxidant capacity.

PMID: 27520356 [PubMed - indexed for MEDLINE]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/10/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/10/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries.

Curr Hypertens Rep. 2017 Oct 06;19(10):83

Authors: Giachini FR, Galaviz-Hernandez C, Damiano AE, Viana M, Cadavid A, Asturizaga P, Teran E, Clapes S, Alcala M, Bueno J, Calderón-Domínguez M, Ramos MP, Lima VV, Sosa-Macias M, Martinez N, Roberts JM, Escudero C, RIVA-TREM

Abstract
Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi-mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic.

PMID: 28986756 [PubMed - in process]

DPP-4 inhibitors and heart failure: a potential role for pharmacogenomics.

Heart Fail Rev. 2017 Oct 06;:

Authors: Krittanawong C, Xanthopoulos A, Kitai T, Branis N, Zhang H, Kukin M

Abstract
There remains an ongoing controversy regarding the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of developing heart failure (HF). In addition, none of the animal studies suggested a mechanism for the DPP-4 inhibitors and HF risk. To date, advances in pharmacogenomics have enabled the identification of genetic variants in DPP-4 gene. Studies have shown that genetic polymorphisms in the gene encoding DPP-4 may be associated with potential pathways involved in HF risk. This review discusses the contradictory findings of DPP-4 inhibitors and HF and a potential role for pharmacogenomics. Pharmacogenomics of DPP-4 inhibitors is promising, and genetic information from randomized control trials is urgently needed to gain a full understanding of the safety of DPP-4 inhibitors and the risk of HF.

PMID: 28986727 [PubMed - as supplied by publisher]

Clinical utility of the low-density Infinium QC genotyping Array in a genomics-based diagnostics laboratory.

BMC Med Genomics. 2017 Oct 06;10(1):57

Authors: Ponomarenko P, Ryutov A, Maglinte DT, Baranova A, Tatarinova TV, Gai X

Abstract
BACKGROUND: With 15,949 markers, the low-density Infinium QC Array-24 BeadChip enables linkage analysis, HLA haplotyping, fingerprinting, ethnicity determination, mitochondrial genome variations, blood groups and pharmacogenomics. It represents an attractive independent QC option for NGS-based diagnostic laboratories, and provides cost-efficient means for determining gender, ethnic ancestry, and sample kinships, that are important for data interpretation of NGS-based genetic tests.
METHODS: We evaluated accuracy and reproducibility of Infinium QC genotyping calls by comparing them with genotyping data of the same samples from other genotyping platforms, whole genome/exome sequencing. Accuracy and robustness of determining gender, provenance, and kinships were assessed.
RESULTS: Concordance of genotype calls between Infinium QC and other platforms was above 99%. Here we show that the chip's ancestry informative markers are sufficient for ethnicity determination at continental and sometimes subcontinental levels, with assignment accuracy varying with the coverage for a particular region and ethnic groups. Mean accuracies of provenance prediction at a regional level were varied from 81% for Asia, to 89% for Americas, 86% for Africa, 97% for Oceania, 98% for Europe, and 100% for India. Mean accuracy of ethnicity assignment predictions was 63%. Pairwise concordances of AFR samples with the samples from any other super populations were the lowest (0.39-0.43), while the concordances within the same population were relatively high (0.55-0.61). For all populations except African, cross-population comparisons were similar in their concordance ranges to the range of within-population concordances (0.54-0.57). Gender determination was correct in all tested cases.
CONCLUSIONS: Our results indicate that the Infinium QC Array-24 chip is suitable for cost-efficient, independent QC assaying in the settings of an NGS-based molecular diagnostic laboratory; hence, we recommend its integration into the standard laboratory workflow. Low-density chips can provide sample-specific measures for variant call accuracy, prevent sample mix-ups, validate self-reported ethnicities, and detect consanguineous cases. Integration of low-density chips into QC procedures aids proper interpretation of candidate sequence variants. To enhance utility of this low-density chip, we recommend expansion of ADME and mitochondrial markers. Inexpensive Infinium-like low-density human chips have a potential to become a "Swiss army knife" among genotyping assays suitable for many applications requiring high-throughput assays.

PMID: 28985730 [PubMed - in process]

Corrigendum.

Pharmacogenomics. 2017 Oct 06;:

Authors:

PMID: 28982277 [PubMed - as supplied by publisher]

Institutional profile: translational pharmacogenomics at the Icahn School of Medicine at Mount Sinai.

Pharmacogenomics. 2017 Oct 06;:

Authors: Scott SA, Obeng AO, Botton MR, Yang Y, Scott ER, Ellis SB, Wallsten R, Kaszemacher T, Zhou X, Chen R, Nicoletti P, Naik H, Kenny EE, Vega A, Waite E, Diaz GA, Dudley J, Halperin JL, Edelmann L, Kasarskis A, Hulot JS, Peter I, Bottinger EP, Hirschhorn K, Sklar P, Cho JH, Desnick RJ, Schadt EE

Abstract
For almost 50 years, the Icahn School of Medicine at Mount Sinai has continually invested in genetics and genomics, facilitating a healthy ecosystem that provides widespread support for the ongoing programs in translational pharmacogenomics. These programs can be broadly cataloged into discovery, education, clinical implementation and testing, which are collaboratively accomplished by multiple departments, institutes, laboratories, companies and colleagues. Focus areas have included drug response association studies and allele discovery, multiethnic pharmacogenomics, personalized genotyping and survey-based education programs, pre-emptive clinical testing implementation and novel assay development. This overview summarizes the current state of translational pharmacogenomics at Mount Sinai, including a future outlook on the forthcoming expansions in overall support, research and clinical programs, genomic technology infrastructure and the participating faculty.

PMID: 28982267 [PubMed - as supplied by publisher]

Studies on para-methoxymethamphetamine (PMMA) metabolite pattern and influence of CYP2D6 genetics in human liver microsomes and authentic samples from fatal PMMA intoxications.

Drug Metab Dispos. 2017 Oct 04;:

Authors: Vevelstad M, Oiestad EL, Nerem E, Arnestad M, Bogen IL

Abstract
Para-methoxymethamphetamine (PMMA) has caused numerous fatal poisonings worldwide and appears to be more toxic than other ring-substituted amphetamines. Systemic metabolism is suggested to be important for PMMA neurotoxicity, possibly through activation of minor catechol metabolites to neurotoxic conjugates. The aim of this study was to examine the metabolism of PMMA in humans, and for this purpose we used human liver microsomes (HLM) and blood samples from three cases of fatal PMMA intoxication. We also examined the impact of CYP2D6 genetics on PMMA metabolism using genotyped HLM isolated from CYP2D6 poor, population average and ultrarapid metabolizers. In HLM, PMMA was metabolized mainly to 4-hydroxymethamphetamine (OH-MA), while low concentrations of para-methoxyamphetamine (PMA), 4-hydroxyamphetamine (OH-A), dihydroxymethamphetamine (di-OH-MA) and oxilofrine were formed. The metabolite profile in the fatal PMMA intoxications were in accordance with the HLM study, with OH-MA and PMA being the major metabolites, while OH-A, oxilofrine, HM-MA and HM-A were detected in low concentrations. A significant influence of CYP2D6 genetics on PMMA metabolism in HLM was found. The catechol metabolite di-OH-MA has previously been suggested to be involved in PMMA toxicity. Our studies show that the formation of di-OH-MA from PMMA was 2-7 times lower than from an equimolar dose of the less toxic drug MDMA, and do not support the hypothesis of catechol metabolites as major determinants of fatal PMMA toxicity. Altogether, the present study revealed the metabolite pattern of PMMA in humans and demonstrated a great impact of CYP2D6 genetics on human PMMA metabolism.

PMID: 28978661 [PubMed - as supplied by publisher]

Lessons Learned From Past Gene-Environment Interaction Successes.

Am J Epidemiol. 2017 Oct 01;186(7):778-786

Authors: Ritz BR, Chatterjee N, Garcia-Closas M, Gauderman WJ, Pierce BL, Kraft P, Tanner CM, Mechanic LE, McAllister K

Abstract
Genetic and environmental factors are both known to contribute to susceptibility to complex diseases. Therefore, the study of gene-environment interaction (G×E) has been a focus of research for several years. In this article, select examples of G×E from the literature are described to highlight different approaches and underlying principles related to the success of these studies. These examples can be broadly categorized as studies of single metabolism genes, genes in complex metabolism pathways, ranges of exposure levels, functional approaches and model systems, and pharmacogenomics. Some studies illustrated the success of studying exposure metabolism for which candidate genes can be identified. Moreover, some G×E successes depended on the availability of high-quality exposure assessment and longitudinal measures, study populations with a wide range of exposure levels, and the inclusion of ethnically and geographically diverse populations. In several examples, large population sizes were required to detect G×Es. Other examples illustrated the impact of accurately defining scale of the interactions (i.e., additive or multiplicative). Last, model systems and functional approaches provided insights into G×E in several examples. Future studies may benefit from these lessons learned.

PMID: 28978190 [PubMed - in process]

Genetic polymorphisms of long non-coding RNA GAS5 predict platinum-based concurrent chemoradiotherapy response in nasopharyngeal carcinoma patients.

Oncotarget. 2017 Sep 22;8(37):62286-62297

Authors: Guo Z, Wang Y, Zhao Y, Jin Y, An L, Wu B, Liu Z, Chen X, Zhou H, Wang H, Zhang W

Abstract
LncRNA GAS5 plays a tumor suppressive role in a variety of human cancers and promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. However, the role of GAS5 in nasopharyngeal carcinoma (NPC) remains elusive. The objective of the present study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in GAS5 on treatment efficacy and toxicity in NPC patients receiving chemoradiotherapy. Three potentially functional SNPs of GAS5 were genotyped in 267 NPC patients and validated in another 238 NPC patients treated with chemoradiotherapy from southern China. Multivariate logistic regression analyses and stratification analyses were used to estimate the association of candidate SNPs and chemoradiotherapy efficacy and toxic reactions. Our results showed that rs2067079 kept a consistent association with severe myelosuppression and severe neutropenia in discovery set (OR=2.403, P=0.009; OR=2.454, P=0.015; respectively), validation set (OR=3.653, P=0.027; OR=4.767, P=0.016; respectively), and combined dataset (OR=1.880, P=0.007; OR=2.079, P=0.005; respectively). rs2067079 CT genotype carriers presented an even more remarkable increased risk of severe myelosuppression (OR=3.878, P=0.003) and severe neutropenia (OR=3.794, P=0.009) in subgroups taking paclitaxel+platinum as concurrent chemoradiotherapy regimen. Besides, we found a gene-does effect of rs6790, with the incidence rate of severe myelosuppression decreased from 23.56% to 17.21% to 10% and the incidence rate of severe neutropenia decreased from 30.4% to 20.9% to 17.1% for rs6790 GG vs GA vs AA genotype carriers. Our results indicate the potential role of lncRNA GAS5 polymorphisms rs2067079 and rs6790 as predictive biomarkers for chemoradiotherapy induced toxic reactions in NPC patients.

PMID: 28977945 [PubMed]

Utility of gene methylation analysis, cytological examination, and HPV-16/18 genotyping in triage of high-risk human papilloma virus-positive women.

Oncotarget. 2017 Sep 22;8(37):62274-62285

Authors: Tian Y, Yuan Wu NY, Liou YL, Yeh CT, Cao L, Kang YN, Wang HJ, Li Y, Chu TY, Li W, Liu X, Zhang Y, Zhou H, Zhang Y

Abstract
In 2015, the American Society for Colposcopy and Cervical Pathology and the Society of Gynecologic Oncology issued interim guidance for the use of a human papillomavirus (HPV) test for primary screening, suggesting triage of women positive for high-risk human papillomavirus (hrHPV) by HPV-16/18 genotyping and cytology for women positive for non-16/18 hrHPV. The design of the present study was based on this interim guidance and analysis of the methylation status of specific candidate genes, which has been proposed as a tool to reduce unnecessary referral following primary HPV screening for cervical cancer. We performed a hospital-based case-control study including 312 hrHPV-positive women. hrHPV genotyping was performed by nested multiplex PCR assay with type-specific primers.Residual cervical cells from liquid-based cytology were used for extraction of genomic DNA for assessment of the methylation status of PAX1, ZNF582, SOX1, and NKX6-1 and HPV genotyping. Combined with HPV-16/18 genotyping, both a dual methylation test for PAX1/ZNF582 and testing for ZNF582 methylation demonstrated 100% association of methylation with pathology results, indicating carcinoma in situ or squamous cell carcinoma. The sensitivity and specificity of the dual methylation test for PAX1/ZNF582 as a reflex test for identification of CIN3+ lesions were 78.85% and 73.55% (odds ratio = 10.37, 95% confidence interval = 4.76-22.58), respectively. This strategy could reduce the number of patients referred for colposcopic examination by 31.3% compared with cytology, and thus provide a feasible follow-up solution in regions where colposcopy is not readily available. This strategy could also prevent unnecessary anxiety in women with hrHPV infection.

PMID: 28977944 [PubMed]