Impact Of Non-genetic Factors Research Articles

Nicotine Gum in Thai Smokers with Different CYP2A6 Enzymes: A Population Pharmacokinetic Analysis

Objective: Despite the popularity of nicotine gum in Thailand, population pharmacokinetics of nicotine gum in the Thai population has not been investigated. This study aimed to develop a population pharmacokinetic (POPPK) model of nicotine and to quantify the effects of genetic and non-genetic factors to nicotine pharmacokinetics. Materials and Methods: Secondary data collected from a previous clinical trial assessing cytochrome P450 2A6 (CYP2A6) genotypes in Thai smokers was investigated. Eighteen participants who had received a single dose of 2 mg nicotine gum were included. Blood samples were collected before, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4.5 and 6 hours after nicotine administration. POPPK analysis was performed using nonlinear mixed effect modelling. Results: One-compartment with 1st order elimination and absorption with 6-transit compartments best described the data. CYP2A6 enzyme activity was a significant covariate on the nicotine clearance. Apparent elimination clearance (CL/F) for a person with 100% CYP2A6 activity was 266.0 L/h. CL/F would be 36.0 L/h in a subject with 0% CYP2A6 activity. However, the impact of non-genetic factors (monthly alcohol consumption, Fagerstrom Test for Nicotine Dependence score and the number of cigarettes per day) on pharmacokinetics of nicotine were not found. Conclusion: This first report on population pharmacokinetics of nicotine gum in Thai smokers provided the pharmacokinetic model and quantified CL/F for smokers with different CYP2A6 genotypes. A markedly lower exposure to nicotine in the Thai population compared to others highlights the need for more studies to ensure the efficacy of nicotine gum in the Thai population.

Impact of non-genetic factors on Sonadi sheep body weight

Impact of non-genetic factors on Sonadi sheep body weight

​Impact of Non-genetic Factors on Kleiber Ratio in Field Flocks of Marwari Goat

Background: The Kleiber ratio in a goat is an important parameter related to feeding and health care. The present study was undertaken to assess the kleiber ratio of 3079 Marwari goats (born from 2016 to 2021) of registered farmers under the All India Coordinated Research Project on goats (Marwari goat field unit) in semi-arid region of Rajasthan. Methods: The linear mixed model used for kleiber ratio estimation included: year of birth, sex, cluster, birth type and age of dam as fixed factors. Result: Overall least-squares means (LSM) for Kleiber ratio (KR) from birth to 3 months (KR1), 3 to 6 months (KR2) and 6 to 12 months (KR3) were 12.89±0.03, 9.69±0.05 and 4.59±0.06, respectively. Year of birth and cluster had highly significant effect on all KR. The birth type had significant on all KR except KR1. The non-significant effect of sex and age of dam were observed on all KR except KR1. The study revealed that the KR was affected by different non-genetic factors. The heritability estimates for KR1, KR2 and KR2 were 0.66±0.28, 0.07±0.07 and 0.54±0.26, respectively.

Engineering Tools for Regulating Hypoxia in Tumour Models.

Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain incurable due to the development of drug resistance, minimal residual disease (MRD) and disease relapse, highlighting an incomplete understanding of the mechanisms underlying these processes. In recent years, the impact of non‐genetic factors on neoplastic transformations has increasingly been acknowledged, and growing evidence suggests that low oxygen (O2) levels (ie hypoxia) in the tumour microenvironment play a critical role in the development and treatment of cancer. As a result, there is a growing need to develop research tools capable of reproducing physiologically relevant O2 conditions encountered by cancer cells in their natural environments in order to gain in‐depth insight into tumour cell metabolism and function. In this review, the authors highlight the importance of hypoxia in the pathogenesis of malignant diseases and provide an overview of novel engineering tools that have the potential to further drive this evolving, yet technically challenging, field of cancer research.

Genetics of hypertrophic cardiomyopathy: Genotype-phenotype correlation

Hypertrophic cardiomyopathy (HCM) has a sarcomeric origin in more than half of cases. Correlations between a mutation presence and the clinical, electrical and echocardiographic phenotype are not clearly characterised. To determine the link for HCM patients between the genotype/phenotype, and the impact of a found mutation. We studied a group of 104 patients with a HCM diagnosis (average age: 56 ± 15 years). Clinical, echocardiographic, electrocardiographic as well as genetic data were evaluated and compared. Genotype-positive patients were more likely to be younger (50,9 ± 17.5 years versus 39,9 ± 17.6, P < 0.01), more often women (56% versus 27%, P < 0.01), had more family history of hypertrophic cardiomyopathy (51% versus 18%, P < 0.001) and an increased incidence of sudden death (2,99 ± 2,83 versus 1,97 ± 1,2, P = 0.03). Echocardiographically, they were less often obstructive ( P < 0.01) and had a reduced left ventricular ejection function ( P = 0.02). Electrically, there was no difference in left ventricular hypertrophy ECG variables or in repolarization problems between the two groups. Genotype-phenotype link for HCM patients is low and both the ECG and the echocardiography are not relevant. The presence of a mutation is associated with an increased risk of sudden death. Genetic testing for HCM patients remains essential considering the impact of non-genetic factors.

Factors affecting milk yield and composition of Tunisian camels (Camelus dromedarius) over complete lactation.

This study aimed to investigate the milk production potential and the impact of nongenetic factors on milk yield and composition of Tunisian dromedary camels. Milk recording and sampling were carried out at monthly intervals over complete lactation for 3years from 95 camels reared in intensive and semi-intensive systems. The overall means of daily milk yield and fat, protein, total solids, and ash contents were 4.21 ± 1.98l/day, 2.45 ± 0.9%, 2.67 ± 0.74%, 10.75 ± 1.41%, and 0.85 ± 0.08%, respectively. The total milk yield was 1388.41 ± 575.46l/lactation for 11months of lactation. The daily milk yield increased regularly throughout lactation until it reached its peak in the 4th month postpartum and then decreased until the 17th month postpartum. The chemical components, except ash, followed an opposite trend to the milk yield. Their minimum contents were recorded during the 7th and 8th months postpartum, while the maximum levels were observed during the 17th month postpartum. Regarding seasonal variation, the highest daily milk yield was recorded during summer (June), whereas the lowest was found in winter (December). In contrast, the maximum and minimum contents of fat and protein were observed during winter (December) and summer (July), respectively. Similarly, total solids content was maximum in January and minimum in August. Parity had no effect on daily milk yield, while all chemical components were higher in milk from primiparous than multiparous camels. Calf sex and management system did not affect the milk yield and composition. These results are useful in order to develop feeding strategies and breeding programs for improving milk production.

Effects of non-genetic factors on the inter-calving period of Nguni cows in South Africa

The purpose of this study was to evaluate the effect of geographical regions of South Africa on the inter-calving period of Nguni cows. Data of Nguni cows (n = 26 681) from 427 Nguni breeders in the Savannah and the Grassland Biomes were statistically analyzed to establish the impact of non-genetic factors on the inter-calving period (ICP) of these cows. Cows with an ICP of less than 315 and above 730 days were removed from the dataset before analysis, to comply with Nguni breed standards. Dam age was included as a covariant. The ICP increased slightly up to 48 months of age, after which a decline was noticed up to the age of 108 months. Cows in the Savannah Biome had a shorter ICP than those studied in the Grassland Biome. Within the Savannah Biome, the ICP of cows was significantly shorter in the Eastern Kalahari Bushveld bioregion than in any other bioregion, while in the Grassland Biome the ICP was significantly shorter for cows calving in the Drakensberg and the Dry Highveld bioregions. In terms of seasons, the ICP of cows bred in spring and summer was significantly shorter than that of cows bred in autumn and winter. Categorization of cows in year groupings indicates significant year effects. Keywords : Biome, bioregion, dam age, reproduction, season

基于非遗传因素对食管癌发病影响的Meta分析

基于非遗传因素对食管癌发病影响的Meta分析

CRISPR Perturbation of Gene Expression Alters Bacterial Fitness under Stress and Reveals Underlying Epistatic Constraints

The evolution of antibiotic resistance has engendered an impending global health crisis that necessitates a greater understanding of how resistance emerges. The impact of nongenetic factors and how they influence the evolution of resistance is a largely unexplored area of research. Here we present a novel application of CRISPR-Cas9 technology for investigating how gene expression governs the adaptive pathways available to bacteria during the evolution of resistance. We examine the impact of gene expression changes on bacterial adaptation by constructing a library of deactivated CRISPR-Cas9 synthetic devices to tune the expression of a set of stress-response genes in Escherichia coli. We show that artificially inducing perturbations in gene expression imparts significant synthetic control over fitness and growth during stress exposure. We present evidence that these impacts are reversible; strains with synthetically perturbed gene expression regained wild-type growth phenotypes upon stress removal, while maintaining divergent growth characteristics under stress. Furthermore, we demonstrate a prevailing trend toward negative epistatic interactions when multiple gene perturbations are combined simultaneously, thereby posing an intrinsic constraint on gene expression underlying adaptive trajectories. Together, these results emphasize how CRISPR-Cas9 can be employed to engineer gene expression changes that shape bacterial adaptation, and present a novel approach to synthetically control the evolution of antimicrobial resistance.

Comment prendre en compte le risque génétique de cancer du sein ? Gènes impliqués et risques tumoraux associés

Our understanding of hereditary forms of breast cancer has made enormous advances over the past 15 years, based on epidemiological and molecular genetic studies, and the development of a vast number of informative genetic markers. These studies have involved women with both familial and sporadic forms of breast cancer. Genetic susceptibility to breast cancer can involve several modes of inheritance: Mendelian inheritance, mostly involving autosomal dominant mutations with high penetrance and a high risk of malignancy (the BRCA1, BRCA2, TP53, PTEN and STK11 genes); dominant mutations associated with a lower risk (ATM, BRIP1, PALB2, etc), and multigenic patterns involving common susceptibility variants, i.e., polymorphisms located within predisposing gene loci (FGFR2, TNRC9, MAP3K1, LSP1, etc.) or intergenic regions. Other predisposing factors remain to be discovered, as genetic factors associated with a high breast cancer risk (BRCA1, BRCA2, TP53, PTEN STK11, etc) are only found in about 20% of genetically screened breast cancer families. So far, only the first class of genes have found clinical applications, guiding the choice of medical or surgical treatment. More refined individual risk profiles will benefit from genome-wide polymorphic DNA variant studies anda better understanding of the impact of non genetic factors, such as the obstetrical and gynaecological history, and mutagen exposure.