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Genetic Polymorphisms Associated with the Neutrophil?Lymphocyte Ratio and Their Clinical Implications for Metabolic Risk Factors.

ABSTRACT: BACKGROUND:The neutrophil?lymphocyte ratio (NLR) is a valuable prognostic or predictive biomarker in various diseases, but the genetic factors that underlie the NLR have not been studied. We attempted to investigate polymorphisms related to NLR phenotype and analyze their ability to predict metabolic risks. METHODS:A genome-wide association study was performed with log-transformed NLR using an Affymetrix Axiom™ KORV1.1-96 Array. Regression models for metabolic risk status were designed using the identified significant single-nucleotide polymorphisms (SNPs). RESULTS:We identified four SNPs near the TMEM116, NAA25, and PTPN11 genes that were associated with the NLR. The top SNP associated with the log-transformed NLR was rs76181728 in TMEM116. A case?control study was performed to analyze the metabolic risks associated with each SNP after adjusting for age, sex, and body mass index (BMI). Three SNPs displayed significant odds ratios (ORs) for increased blood pressure and increased waist circumference. In the regression model for metabolic syndrome, rs76181728 showed a significant association (OR = 1.465, 95% confidence interval (CI) = 1.091?1.969, P = 0.011) after adjustment for the NLR phenotype. CONCLUSIONS:We identified four novel SNPs that are associated with the NLR in healthy Koreans. SNPs in relevant genes might therefore serve as biomarkers for metabolic risks.

SUBMITTER: Park B

PROVIDER: S-EPMC6111840 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Genetic Polymorphisms Associated with the Neutrophil⁻Lymphocyte Ratio and Their Clinical Implications for Metabolic Risk Factors.

Park Boram B Choe Eun Kyung EK Kang Hae Yeon HY Shin Eunsoon E Lee Sangwoo S Won Sungho S

Journal of clinical medicine 20180808 8

<h4>Background</h4>The neutrophil⁻lymphocyte ratio (NLR) is a valuable prognostic or predictive biomarker in various diseases, but the genetic factors that underlie the NLR have not been studied. We attempted to investigate polymorphisms related to NLR phenotype and analyze their ability to predict metabolic risks.<h4>Methods</h4>A genome-wide association study was performed with log-transformed NLR using an Affymetrix Axiom™ KORV1.1-96 Array. Regression models for metabolic risk status were des ...[more]

PMID: 30096757

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Project description:Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR.Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52).Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.

Dataset Information

Genetic Polymorphisms Associated with the Neutrophil?Lymphocyte Ratio and Their Clinical Implications for Metabolic Risk Factors.

Publications

Genetic Polymorphisms Associated with the Neutrophil⁻Lymphocyte Ratio and Their Clinical Implications for Metabolic Risk Factors.

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