Candidate Gene Polymorphisms Research Articles

Associations between skin rash, treatment outcome, and single nucleotide polymorphisms in head and neck cancer patients receiving the EGFR-inhibitor zalutumumab: results from the DAHANCA 19 trial

Purpose To study the associations between development of moderate to severe skin rash, clinical outcome, and single nucleotide polymorphisms (SNPs) in candidate genes in head and neck cancer patients from the DAHANCA 19 trial receiving the EGFR-inhibitor zalutumumab concurrently with radiation treatment. Material and methods 310 patients were included from the zalutumumab-arm of the DAHANCA 19 study. Nine SNPs in the candidate genes EGFR, EGF, AREG, FCGR2A, FCGR3A, and CCND1 were successfully determined in 294 patients. Clinical endpoints were moderate to severe skin rash within the first 3 weeks of treatment, loco-regional failure (LRF), disease-specific survival (DSS), and overall survival (OS). Results During the first 3 weeks of treatment, 86% of the patients experienced any grade of rash and 17% experienced a moderate to severe rash. Development of moderate to severe rash was not associated with LRF or DSS but was associated with improved OS, HR 0.40 (95% CI: 0.19–0.82). The effect was similar for patients with p16-negative or p16-positive tumors (p = .90). After adjustment for comorbidity and performance status, the minor alleles of SNPs rs9996584 and rs13104811 located near the AREG gene were significantly associated with increased risk of moderate to severe rash with per-allele odds ratios of 1.61 (1.01–2.54) and 1.56 (1.00–2.44). SNP rs11942466 located close to rs9996584 had a borderline significant association, and none of the other SNPS were significantly associated with risk of skin rash. Conclusions Moderate to severe skin rash after zalutumumab during radiation treatment was associated with improved OS, independent of HPV/p16-status. Genetic variants in AREG (member of the EGF family) may be associated with increased risk of skin rash.

Impact of NTRK2, DRD2 and ACE polymorphisms on prolactin levels in antipsychotic-treated patients with first-episode psychosis.

Hyperprolactinemia is a common side-effect of antipsychotics (APs), which may trigger serious secondary problems and compromise the adherence to treatment which is crucial for prognosis, especially in patients presenting with a first-episode of psychosis (FEP). We evaluated, in some cases for the first time, the effect of polymorphisms in multiple candidate genes on serum prolactin (PRL) levels in an AP-treated FEP cohort recruited in the multicenter PEPs study (Phenotype - genotype and environmental interaction; Application of a predictive model in first psychotic episodes). PRL concentration was measured in serum from 222 patients. A total of 167 polymorphisms were selected in 23 genes. Genetic association analysis was performed in the whole sample and also in homogenous subgroups of patients treated with APs with a high (N = 101) or low risk (N = 95) of increasing PRL release, which showed significant differences in their PRL levels. After Bonferroni correction, polymorphisms in NTRK2, DRD2 and ACE genes were associated with PRL concentration. Our results give more support to the impact of DRD2, but also of other genes related to dopamine availability such as ACE. Moreover, this study provides the first evidence for the involvement of NTRK2, which suggests that pathways other than the ones related to dopamine or serotonin may participate in the AP-related PRL levels.

Genetic linkage map and QTL identification for adventitious rooting traits in red gum eucalypts.

The eucalypt species, Eucalyptus tereticornis and Eucalyptus camaldulensis, show tolerance to drought and salinity conditions, respectively, and are widely cultivated in arid and semiarid regions of tropical countries. In this study, genetic linkage map was developed for interspecific cross E. tereticornis × E. camaldulensis using pseudo-testcross strategy with simple sequence repeats (SSRs), intersimple sequence repeats (ISSRs), and sequence-related amplified polymorphism (SRAP) markers. The consensus genetic map comprised totally 283 markers with 84 SSRs, 94 ISSRs, and 105 SRAP markers on 11 linkage groups spanning 1163.4cM genetic distance. Blasting the SSR sequences against E. grandis sequences allowed an alignment of 64% and the average ratio of genetic-to-physical distance was 1.7 Mbp/cM, which strengths the evidence that high amount of synteny and colinearity exists among eucalypts genome. Blast searches also revealed that 37% of SSRs had homologies with genes, which could potentially be used in the variety of downstream applications including candidate gene polymorphism. Quantitative trait loci (QTL) analysis for adventitious rooting traits revealed six QTL for rooting percent and root length on five chromosomes with interval and composite interval mapping. All the QTL explained 12.0-14.7% of the phenotypic variance, showing the involvement of major effect QTL on adventitious rooting traits. Increasing the density of markers would facilitate the detection of more number of small-effect QTL and also underpinning the genes involved in rooting process.

Genomics of physiological adaptations of two milkweed species (Asclepias) in their hybrid zone

Speciation is the source of diversity on the planet, but the genomic mechanisms that lead to the reproductive isolating barriers between populations that cause speciation are not well understood. Here we are studying the genomic differentiation between two species of milkweed that grow in the Western (Asclepias speciosa) and Eastern United States (A. syrica). In addition to different geographic locations, these species have diverged in a number of important phenotypes, including: production of secondary metabolites, flower morphology, and drought resistance. In the central US, these species have come into secondary contact and sometimes form hybrids in the wild. We are interested in quantifying the amount of gene flow between these species and identifying genomic locations that may be indicative of local adaptation within populations and reproductive isolation between species.To compare these species of milkweed, we isolated DNA from A. speciousa, A. syrica, and individuals that displays intermediate phenotypes from the hybridization zone. We extracted and isolated genomic DNA and sequenced their genomes with Oxford Nanopore technology. With the aligned genomes, we will be able to compare polymorphisms in these species and begin to quantify the amount of gene flow between them. We will also identify polymorphisms in candidate genes and pathways that may have led to ecological specialization between these species.Support or Funding InformationSouth Dakota EPSCoR IIA‐1355423South Dakota BRIN P20GM 103443This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

EPIDEMIOLOGICAL, TOXICOLOGICAL AND MOLEСULAR-GENETIC ASPECTS OF ENDOCRINE DISRUPTING CHEMICALS IN THE CHEMICAL SAFETY PROBLEM

The literature review has shown the problem of endocrine disrupting chemicals (EDC) to be associated with their wide distribution in the environment, the abundance, and variety of the chemical structure. Three leading mechanisms of EDCs action are identified as follows: imitation of the naturally occurring hormones action, blocking of receptors within the target cells of hormones, the impact of their kinetics in the body. Epidemiological studies indicate an increase in diseases caused by a disorder of the hormonal system. They are associated with the effect of EDCs. Substances that are completely dissimilar in chemical structure can cause the same effects. According to WHO [6], it is impossible, based on the chemical structure, to determine whether a substance is a disruptor of the endocrine system. However, some structural features determine the estrogenic, thyreogenic and glucocorticoid activity of chemicals. Hence, the need to differentiate the specific (primary) effect of a chemical substance on the endocrine system and the indirect (secondary) effect on it via other mechanisms comes to the fore. In own research, specific mechanisms were shown to be determined in the experiment when studying the complexity of effects, taking into account the processes of adaptation and decompensation, and identifying the effects manifested with the lowest doses. One of the methodological approaches can be the developed “structure-biotransformation-activity” prediction system aimed at revealing the primary types of effects: using quantum-chemical calculations and the plausible reasoning class (called the JSM-reasoning in honour of John Stuart Mill) logico-combinatorial method, it was possible to identify structural fragments of substances responsible for the manifestation of carcinogenic, allergenic effects, methemoglobin formation, etc. The results of clinical studies show the use of pharmacological drugs as models for in vivo study of the effects of EDC to allow not only studying atypical mechanisms of the impact of EDCs from the point of view of molecular genetics but also to predict the individual susceptibility to them taking into account polymorphism of candidate genes. The EDCs problem poses the need for a complex of interdisciplinary research, including three main relationships: exposure assessment-biomonitoring data-the prevalence of endocrine-dependent diseases, taking into account the qualitative and quantitative contribution of individual endocrine disrupters to the development of an ecologically dependent endocrine pathology using molecular genetic methods.

Identificación de factores de riesgo genéticos asociados a la enfermedad vascular cerebral de tipo isquémico en jóvenes mexicanos

IntroductionNumerous polymorphisms in candidate genes coding for haemostatic system proteins have been proposed as risk factors for thrombosis. MethodsWe performed a case-control study of consecutive ischaemic stroke survivors aged ≤ 45 years, treated at our neurology department from 2006 to 2014. Polymerase chain reaction–restriction fragment length polymorphism identified the following polymorphisms: Thr325Ile and Ala147Thr in TAFI, 4G/5G in PAI-1, PLA1/A2 in platelet glycoprotein IIb/IIIa, Glu298Asp in eNOS, and C677T in 5,10-MTHFR. A multivariate logistic regression analysis was performed to evaluate the independent risk of stroke. Results204 cases and 204 age- and sex-matched controls were included in the study. Clinical and genetic variables associated with ischaemic stroke were hypertension (P=.03), tobacco use (P=.02), and the polymorphisms Glu298Asp (genotype: P=.001, allele frequency: P=.001) and C677T (genotype: P=.01); the Ala147Thr, Thr325IIe, 4G/5G, and PLA1/A2 mutations were not associated with ischaemic stroke. The 298Asp (P=.03) and T (P=.01) alleles, hypertension (P=.03), tobacco use (P=.01) and family history of stroke (P=.04) were identified as independent risk factors. ConclusionsThe polymorphisms Glu298Asp and C677T, affecting the eNOS and 5,10-MTHFR enzymes, respectively, and smoking, hypertension, and family history of stroke were associated with ischaemic stroke in young Mexican patients; this was not the case for the Thr325Ile, Ala147Thr, 4G/5G, and PLA1/A2 polymorphisms of the genes coding for fibrinolytic proteins and platelet receptors.

Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth

To evaluate the association of magnesium sulfate (MgSO4) exposure and candidate gene polymorphisms with adverse neurodevelopmental outcomes following preterm birth. We performed a nested case-control analysis of a randomized trial of maternal MgSO4 before anticipated preterm birth for the prevention of cerebral palsy (CP). Cases were children who died within 1 year of life or were survivors with abnormal neurodevelopment at age 2 years. Controls were race- and sex-matched survivors with normal neurodevelopment. We analyzed 45 candidate gene polymorphisms in inflammation, coagulation, and vascular regulation pathways and their association with (1) psychomotor delay, (2) mental delay, (3) CP, and (4) combined outcome of death/CP. Logistic regression analyses, conditional on maternal race and child sex, and adjusted for treatment group, gestational age at birth and maternal education, were performed. Four hundred and six subjects, 211 cases and 195 controls, were analyzed. The strongest association was for IL6R (rs 4601580) in which each additional copy of the minor allele was associated with an increased risk of psychomotor delay (adjusted odds ratio 3.3; 95% confidence interval, 1.7-6.5; p < 0.001). Candidate gene polymorphisms are associated with death and adverse neurodevelopmental outcomes following preterm birth. MgSO4 may abrogate this genotype association for some loci.

Environmental and genetic control of cold tolerance in the Glanville fritillary butterfly.

Thermal tolerance has a major effect on individual fitness and species distributions and can be determined by genetic variation and phenotypic plasticity. We investigate the effects of developmental and adult thermal conditions on cold tolerance, measured as chill coma recovery (CCR) time, during the early and late adult stage in the Glanville fritillary butterfly. We also investigate the genetic basis of cold tolerance by associating CCR variation with polymorphisms in candidate genes that have a known role in insect physiology. Our results demonstrate that a cooler developmental temperature leads to reduced cold tolerance in the early adult stage, whereas cooler conditions during the adult stage lead to increased cold tolerance. This suggests that adult acclimation, but not developmental plasticity, of adult cold tolerance is adaptive. This could be explained by the ecological conditions the Glanville fritillary experiences in the field, where temperature during early summer, but not spring, is predictive of thermal conditions during the butterfly's flight season. In addition, an amino acid polymorphism (Ala‐Glu) in the gene flightin, which has a known function in insect flight and locomotion, was associated with CCR. These amino acids have distinct biochemical properties and may thus affect protein function and/or structure. To our knowledge, our study is the first to link genetic variation in flightin to cold tolerance, or thermal adaptation in general.

Linking dendroecology and association genetics in natural populations: Stress responses archived in tree rings associate with SNP genotypes in silver fir (Abies alba Mill.).

Genetic association studies in forest trees would greatly benefit from information on the response of trees to environmental stressors over time, which can be provided by dendroecological analysis. Here, we jointly analysed dendroecological and genetic data of surviving silver fir trees to explore the genetic basis of their response to the iconic stress episode of the 1970s and 1980s that led to large-scale forest dieback in Central Europe and has been attributed to air pollution. Specifically, we derived dendrophenotypic measures from 190 trees in the Bavarian Forest that characterize the resistance, resilience and recovery during this growth depression, and in the drought year in 1976. By focusing on relative growth changes of trees and by standardizing the dendrophenotypes within stands, we accounted for variation introduced by micro- and macroscale environmental differences. We associated the dendrophenotypes with single nucleotide polymorphisms (SNPs) in candidate genes using general linear models (GLMs) and the machine learning algorithm random forest with subsequent feature selection. Most trees at our study sites experienced a severe growth decline from 1974 until the mid-1980s with minimum values during the drought year. Fifteen genes were associated with the dendrophenotypes, including genes linked to photosynthesis and drought stress. With our study, we show that dendrophenotypes can be a powerful resource for genetic association studies that permit to account for micro- and macroenvironmental variation when data are derived from natural populations. We call for a wider collaboration of dendroecologists and forest geneticists to integrate individual tree-level dendrophenotypes in genetic association studies.

Genetic Associations with Indoor Tanning Addiction

Abstract Some young people are prone to develop addiction to indoor tanning along with psychiatric comorbidity. This study examined genetic hypotheses that liabilities in neurobiological addiction reward pathways influence risk of indoor tanning addiction and are affected by psychiatric comorbidity. Methods: Data were from an observational study investigating factors associated with indoor tanning addiction in a community sample of non-Hispanic white women ages 18–30 years with a history of indoor tanning in the past year. A total of 295 participants completed self-report measures and provided DNA samples. DNA samples were genotyped and analyzed for 36 single nucleotide polymorphisms (SNPs) in candidate genes involved in hypothesized addiction reward pathways (e.g., opioid and dopamine receptor genes). Self-report measures included indoor tanning frequency and dependence symptoms, appearance beliefs, and depressive symptoms. Results: Over 20% of the sample screened positive for indoor tanning addiction. Two SNPs in the DRD2 dopamine receptor gene, rs4436578 and rs4648318, were significantly associated (P &amp;lt; 0.05) with indoor tanning addiction after multiple testing adjustment using the false discovery rate. In logistic regression analyses adjusting for indoor tanning frequency, appearance beliefs, and depressive symptoms, homozygous major allele genotypes for both SNPs were associated with indoor tanning addiction (Odds Ratio [OR] 2.29, 95% Confidence Interval [CI] 1.11–4.77, and OR 1.95, 95% CI, 1.02–3.72, respectively). The major allele genotypes for both SNPs also interacted with depressive symptoms to influence the risk of indoor tanning addiction: OR 7.03, 95% CI, 3.26–15.19, OR 4.35, 95% CI, 2.06–9.20, respectively. Conclusions: This study is among the first to demonstrate SNPs in the DRD2 dopamine receptor gene are associated with indoor tanning addiction. Our findings demonstrate young women with risk-conferring genotypes and exhibiting depressive symptoms are at especially high risk. These data can inform personalized interventions tailored to neurobiological and behavioral differences to prevent melanoma and nonmelanoma skin cancer.

Pharmacogenomics of Hypertension and Preeclampsia: Focus on Gene-Gene Interactions.

Hypertension is a leading cause of cardiovascular mortality, but only about half of patients on antihypertensive therapy achieve blood pressure control. Preeclampsia is defined as pregnancy-induced hypertension and proteinuria, and is associated with increased maternal and perinatal mortality and morbidity. Similarly, a large number of patients with preeclampsia are non-responsive to antihypertensive therapy. Pharmacogenomics may help to guide the personalized treatment for non-responsive hypertensive patients. There is evidence for the association of genetic variants with variable response to the most commonly used antihypertensive drugs. However, further replication is needed to confirm these associations in different populations. The failure to replicate findings from single-locus association studies has prompted the search for novel statistical methods for data analysis, which are required to detect the complex effects from multiple genes to drug response phenotypes. Notably, gene–gene interaction analyses have been applied to pharmacogenetic studies, including antihypertensive drug response. In this perspective article, we present advances of considering the interactions among genetic polymorphisms of different candidate genes within pathways relevant to antihypertensive drug response, and we highlight recent findings related to gene–gene interactions on pharmacogenetics of hypertension and preeclampsia. Finally, we discuss the future directions that are needed to unravel additional genes and variants involved in the responsiveness to antihypertensive drugs.

Association of single nucleotide polymorphisms in fat metabolism candidate genes with fatty acid profiles of muscle and subcutaneous fat in heavy pigs

Dietary and organoleptic qualities of pork products are largely influenced by the profiles of fatty acids (FAs) of meat and fat. The objective of this work was to investigate the potential associations between FA profile in subcutaneous adipose (back fat and leg fat) and muscular (longissimus dorsi and biceps femoris) tissues in heavy pigs (n = 129, 9-month-old) with single nucleotide polymorphisms (SNPs) in six candidate genes involved in fat metabolism: Stearoyl-CoA desaturase (SCD), Diacylglycerol acyltransferase 1 and 2 (DGAT1 &DGAT2), Microsomal Triglyceride Transfer Protein (MTTP), Fatty Acid Synthase (FASN) and Heart- fatty acid binding protein (H-FABP). Preliminary results suggest a putative association between MTTP, DGAT2 and FASN and the FA content in both fat and meat, whereas between DGAT1, SCD and H-FABP the association was found in adipose tissue only. However, the effect of the analyzed genes, needs to be verified in a larger and better characterized pig population to support the hypothesized associations with FA content.

Candidate gene analysis in the São Paulo Epidemiologic Sleep Study (EPISONO) shows an association of variant in PDE4D and sleepiness

IntroductionSleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D). MethodsAdults (N = 918) from the general population who were a part of the São Paulo Epidemiologic Sleep Study (EPISONO) in São Paulo, Brazil, were genotyped using Human Omni Express BeadChip array. The average age was 42 ± 14.5 years, subjects had a mean body mass index (BMI) of 26.9 ± 5.4 kg/m2, and 44% were male. Based on the Epworth Sleepiness Scale (ESS), subjects were classified as having sleepiness (ESS ≥ 10) or no sleepiness (ESS < 10). Logistic regression models were used to examine the associations with SNPs within candidate genes and sleepiness, adjusting for age, gender, BMI, Apnea–Hypopnea Index (AHI), total sleep time, and ancestry informative principal components (PCs). Complementary analyses using linear regression to assess the relationship between SNPs and continuous ESS were performed. ResultsWe observed a novel association between the C allele of the rs12522161 SNP on PDE4D and a decreased likelihood of sleepiness, controlling for covariates and ancestry [OR (95% CI) = 0.64 (0.50, 0.81); p = 0.0002]. ConclusionWe present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.

ROLE OF HELICOBACTER PYLORI AND HOST GENE POLYMORPHISMS IN GASTRIC CARCINOGENESIS IN A KAZAKHS

Emerging evidence indicated that common polymorphisms of TNF-α, IL1B, IL10, TP53, CD14, TLR4 genes might impact individual susceptibility to gastric cancer. Moreover, Helicobacter pylori plays an important role, provoking an increased susceptibility to the development of gastric pathologies. However, the results are still inconclusive, and specific alleles vary in different populations. We conducted a study in the Kazakh population of the Northern region of Kazakhstan to identify potential risks or protective associations of SNP with gastric cancer, or H. pylori infection. We analyzed the association of SNPs in TNF-α (rs1800629 G/A), IL1B (rs16944 A/G), IL10 (rs1800872 G/T, rs1800871 G/A, rs1800896 A/C), TP53 (rs1042522 A/G), CD14 (rs2569190 G/A), and TLR4 (rs4986790 A/G, rs4986791 C/T) genes. We included cases with gastric cancer in a hospital-based Kazakh population (158 cases and 181 cancer-free controls). Identification of Helicobacter pylori was carried out by microbiological methods from biopsy specimens. Genotyping of the extended panel of polymorphisms of candidate genes was performed on the Quant Studio 12K Flex (Life Technologies). To estimate relative risk, odds ratio (OR) and 95% confidence interval (CI) were calculated, and P value 0.05 was considered statistically significant. We found that the polymorphisms of TP53 (rs1042522 A/G, OR: 2.32, 95% CI: 1.41-3.82, P-value=0.0009), CD14 (rs2569190 G/A, OR: 0.59, 95% CI: 0.36 - 0.96, P-value=0.035), and TLR4 (rs4986790 A/G, OR: 0.43, 95% CI: 0.19 - 0.95, P-value=0.038) are associated with gastric cancer risk. No significant association was observed between variant genotype polymorphisms of TNF-α, IL1B, IL10, TLR4 (ID: rs4986791) genes and gastric cancer risk. Further analyzes to assess the combined effect of TP53 rs1042522, CD14 rs2569190 and TLR4 rs4986791 and H. pylori infection on GC risk did not reveal significant associations. Our results testify to markers of GC risk among Kazakhs and may be the first step towards new approaches to diagnosis and prognosis in Kazakhstan.

Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.

Reproductive traits are of the utmost importance for any livestock farming, but are difficult to measure and to interpret since they are influenced by various factors. The objective of this study was to detect associations between known polymorphisms in candidate genes related to sexual precocity in Nellore heifers, which could be used in breeding programs. Records of 1,689 precocious and non-precocious heifers from farms participating in the Conexão Delta G breeding program were analyzed. A subset of single nucleotide polymorphisms (SNP) located in the region of the candidate genes at a distance of up to 5 kb from the boundaries of each gene, were selected from the panel of 777,000 SNPs of the High-Density Bovine SNP BeadChip. Linear mixed models were used for statistical analysis of early heifer pregnancy, relating the trait with isolated SNPs or with haplotype groups. The model included the contemporary group (year and month of birth) as fixed effect and parent of the animal (sire effect) as random effect. The fastPHASE® and GenomeStudio® were used for reconstruction of the haplotypes and for analysis of linkage disequilibrium based on r2 statistics. A total of 125 candidate genes and 2,024 SNPs forming haplotypes were analyzed. Statistical analysis after Bonferroni correction showed that nine haplotypes exerted a significant effect (p<0.05) on sexual precocity. Four of these haplotypes were located in the Pregnancy-associated plasma protein-A2 gene (PAPP-A2), two in the Estrogen-related receptor gamma gene (ESRRG), and one each in the Pregnancy-associated plasma protein-A gene (PAPP-A), Kell blood group complex subunit-related family (XKR4) and mannose-binding lectin genes (MBL-1) genes. Although the present results indicate that the PAPP-A2, PAPP-A, XKR4, MBL-1 and ESRRG genes influence sexual precocity in Nellore heifers, further studies are needed to evaluate their possible use in breeding programs.

Signatures of Selection From Candidate Gene Polymorphisms Panel in Five Zebu Breeds

ABSTRACT The signals of selection using candidate genes polymorphism were studied in five zebu breeds of Mexico. Three loci from GHRH and complementarily Steroyl Co Desaturase F762, Dopamine Beta Hydroxilase 17299, and LEP3272 were identified under selection. Findings depict Zebu selection pressure mainly on Brahman breed resulting in a divergent structure pattern.

An exploratory study of candidate gene(s) for Delirium Tremens: Adding the new cholinergic dimension to the conundrum.

Delirium Tremens (DT) is the most severe form of alcohol withdrawal syndrome, with a potential risk of mortality. Search for the predictors of DT led to study of candidate genes, with inconsistent and inconclusive results. This study aimed to explore the association of various candidate gene polymorphisms and DT in a case-control design. This was a genetic association study with a case control design. Two hundred ten Alcohol dependent (AD) male subjects and 200 age matched controls were recruited. DT was diagnosed with the help of Semi-structured Assessment for Genetics of Alcoholism. SNP genotyping was done using TaqMan assay by real time PCR (q-PCR). T allele carrying status (GT and TT) [rs1824024] of muscarinic cholinergic receptor 2 (CHRM2) was found to be significantly associated with DT. When compared to the general population, this genetic polymorphism was not found to be more common in alcohol dependence per se, which excludes the possibility of spurious association between CHRM2 and DT. Withdrawal seizure was more common in the DT group and came out to be one of the important predictors of DT. However, the genetic association was found to be specific for DT, not related to withdrawal seizures. The present research added a new cholinergic dimension in the genetic association and biological mechanism of DT.

Polymorphism Candidate Genes of Indigenous Lien Minh Chickens

Lien Minh chicken is an indigenous breed with several favorable properties, such as high productivity and good meat quality, and is associated with the economic development of the people in the Lien Minh village, Cat Hai, Hai Phong. The objective of the current research was to investigate the single nucleotide polymorphisms (SNPs) of candidate genes, which might be associated with broodiness and egg production traits. Ninety Lien Minh chicken individuals were genotyped for five SNPs of chicken prolactin (PRL), Vasoactive Intestinal Peptide (VIP), neuropeptide Y gene (NPY), growth hormone (GH), and growth hormone receptor (GHR) genes. Blood samples were used for DNA extraction and then for genotyping by the PCR-RFLP method. The allele frequencies obtained were as follows: 0.19 and 0.81 for alleles C and T (PRL-C2161G), respectively; in VIP (G5138982T), 0.55 for the G allele and 0.45 for T; in GH-SacI (the intron 4), 0.02 for A and 0.98 for B; and in GHR-NspI, 0.82 for C and 0.18 for T. The NPY gene (four nucleotide indel) had the frequencies of 0.86 for I and 0.14 for D. The four studied polymorphic loci (PRL, VIP, NPY, and GH) were in Hardy-Weinberg equilibrium in the Lien Minh chicken population. These are the initial results, which can be used to analyze the correlation of molecular markers and egg production traits in Lien Minh chickens.

GSTP1 Ile105Val polymorphism might be associated with the risk of radiation pneumonitis among lung cancer patients in Chinese population: A prospective study.

Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conducted a prospective study to evaluate the associations between functional SNPs and risk of RP.Methods: We recruited a total of 149 lung cancer patients who had received intensity modulated radiation therapy (IMRT). GSTP1 and XRCC1 were genotyped using the SurPlexTM-xTAG method in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Cox proportional hazard regression was performed to identify clinical variables and SNPs associated with risk of RP grade ≥ 2, using univariate and multivariate analysis, respectively.Results: With a median follow-up of 9 months, the incidence of RP of grade ≥ 2 was 38.3%. A predicting role in RP was observed for the GSTP1 SNP (adjusted hazard ratio 3.543; 95% CI 1.770-7.092; adjusted P< 0.001 for the Ile/Val and Val/Val genotypes versus Ile/Ile genotype). Whereas, we found that patients with XRCC1 399Arg/Gln and Gln/Gln genotypes had a lower risk of RP compares with those carrying Arg/Arg genotype (adjusted HR 0.653; 95% CI 0.342-1.245), but with no statistical significance observed (adjusted P = 0.195).Conclusions: Our results suggested a novel association between GSTP1 SNP 105Ile/Val and risk of RP development, which suggests the potential use of this genetic polymorphism as a predictor of RP. In addition, genetic polymorphisms of XRCC1 399Arg/Gln may also be associated with RP.

The clinical, personality, and genetic correlates of binge drinking: A controlled association study from India

Background and Objectives: Reasonable amount of literature has been accumulated over the years to indicate that the binge drinkers might be different from the group which does not have any history of binging. Only a handful of research demonstrated genetic predisposition for binging. Materials and Methods: This was a clinic-based association study with a case–control design. Two hundred and ten alcohol dependence cases were recruited. Binge drinking was diagnosed using Semi-structured Assessment for Genetics of Alcoholism-II-. Structured instruments were used for the assessment of impulsivity, and novelty seeking traits. single nucleotide polymorphism genotyping was done using Taqmann assay by real-time quantitative polymerase chain reaction (q-PCR) using Taqman assay (ABI 7500) fast real-time PCR system. Results: Comparison of clinical characteristics revealed an earlier age of onset of alcohol use and dependence, significantly more number of accidental injuries, emotional problems, and history of delirium tremens among the binge drinking group. The mean score in the extravagance subscale, overall novelty seeking scale, subscales of nonplanning, and attentional impulsiveness were significantly more among the binge drinkers. With regard to the candidate gene polymorphism (rs25531), short (S) allele of serotonin transporter was observed to be associated with the binge drinking group. Conclusion: Association of impulsiveness and novelty seeking is a new and important finding, indicating the role of personality traits to increase the vulnerability toward binge drinking. The association with the S allele, although is a replication of previous results, is nevertheless important as our study is from a different ethnic population.