Relationship Of Gene Polymorphisms Research Articles

The role of polymorphism of the epidermal growth factor gene in the formation of severe manifestations of skin toxicity caused by the use of EGFR inhibitors

Epidermal growth factor receptor (EGFR) inhibitors are widely used to treat various types of cancer, such as non-small cell lung cancer, head and neck cancer, breast cancer, pancreatic cancer, colorectal cancer. During treatment, class-mediated effects such as skin toxicity, interstitial lung disease, hepatotoxicity, ocular toxicity, hypomagnesemia, stomatitis, and diarrhea may occur. The role of epidermal growth factor and its receptors in the vital activity of keratinocytes is key. Dermatological undesirable effects occur in 60–90% of patients, and often persist throughout the entire period of EGFR inhibitor therapy.
 Currently, studies of biomarkers predicting the severity of skin complications of EGFR inhibitor therapy are extremely limited. Thus, it is relevant to study genetic markers reliably associated with the development of severe skin toxicity against the background of EGFR inhibitor therapy, because the EGFR signaling pathway is important for maintaining normal physiological function of the skin. The development of severe skin reactions leads to a reduction in the dose or discontinuation of EGFR inhibitors in the treatment of cancer. Recently, progress has been made in studies of the cutaneous toxicity of EGFR inhibitors.
 Here we briefly describe the mechanism of skin toxicity caused by EGFR inhibitors, current data on the relationship of gene polymorphism and severity of manifestations of undesirable dermatological phenomena.

АССОЦИАЦИИ ПОЛИМОРФНЫХ ВАРИАНТОВ ГЕНА СОМАТОТРОПИНА С ХОЗЯЙСТВЕННО-ЦЕННЫМИ ПОКАЗАТЕЛЯМИ КОРОВ

Currently, marker genes are often used in dairy cattle breeding. Scientists are studying the relationship of gene polymorphism with such economically useful traits as milk productivity, productive longevity, growth, development, etc. The short period of the economic use of cows and the late intake of live weight necessary for insemination cause economic losses to agricultural organizations. The goal of the research was to study the relationship of the polymorphism of the somatotropin gene with live weight during the first insemination and productive longevity of cows. The study was conducted in the Sverdlovsk region on cattle of Holstein Black-Motley breed in 2018–2019. Two samples were formed: heifers and retired cows genotyped by the somatotropin gene. In animals, LV-somatotropin gene polymorphism was determined. The determination of polymorphism included the following steps: DNA isolation, polymerase chain reaction (PCR), restriction enzyme production, restriction products run on an agarose gel, visualization using a transilluminator. The research results were processed using IBM SPSS Statistics 23 software,and the reliability criterion was analyzed. LV-polymorphism is represented by three genotypes: LL,LV and VV. The authors studied the frequency of genotypes in the population of holsteinized cattle. It was revealed that the LL genotype is widely represented in the population – 77.2%, animals with the LV genotype are found more rarely – 22.2%. The VV genotype is extremely rare in the population – 0.6%. It was also revealed that the L allele is a common population allele – 88.3%. In the course of studying the relationship of LV polymorphism with live weight during the first insemination, it was found that animals with the LL genotype grow faster and reach the live weight necessary for fruitful insemination earlier. At the same age, heifers with the LV genotype had a mass of 400 kg, with those with the LL genotype – 9 kg more at p ≤ 0.01. When studying the effect of somatotropin gene genotypes on productive longevity, it was found that cows with the LV genotype have a longer economic use. The difference with peers with the LL genotype was 0.5 lactations at p ≤ 0.05. As a result of the studies, it can be concluded that the LL and LV genotypes are the desired option for the holsteinized cattle population. The LL genotype is associated with growth and development, and LV – with productive longevity.

Relationship of gene polymorphism with the nature of target organ damage in patients with arterial hypertension

Objective: to assess the relationship of polymorphism of the main genes involved in the pathogenesis of arterial hypertension (AH) with indicators reflecting the state of target organs in the group of patients with arterial hypertension.Material and methods: we examined 100 patients with arterial hypertension who underwent standard diagnostic procedures, as well as molecular genetic research.Results: in patients with arterial hypertension statistically significant associations of AGTR2, GNB3, and NOS3 gene polymorphism with left ventricular hypertrophy, CYP11B2 and NOS3 gene polymorphism with left ventricular diastolic dysfunction, and NOS3 gene polymorphism with increased vascular wall stiffness were found (p < 0.05).Conclusions: the results of the study indicate that patients with arterial hypertension are a genetically heterogeneous group in terms of the relationship of specific gene polymorphism with indicators that characterize the state of target organs. The use of genetic approaches is promising for early screening of patients with arterial hypertension, belonging to the high-risk group, in order to ensure timely and effective organoprotection.

The relationship of gene polymorphism with the heart failure risk in patients with hypertension and high adherence to treatment

Aim. To determine the heart failure (HF) risk in patients with hypertension (HTN) and high adherence to treatment, depending on the blood concentration of the N-terminal pro-brain natriuretic peptide (NT-proBNP) and gene polymorphism. Material and methods. The study included 232 patients with HTN without a verified diagnosis of HF. The mean age was 46,13±8,21 years. Patients were evaluated for genotypes by following markers: AGT Thr174Met rs4762, GNB3 C825T rs5443, MTHFR C677T rs1801133, MTRR Ile22Met rs1801394, ApoE Cys130Arg rs 429358, PPAR α G/C rs425377. We also assessed ejection fraction, diastolic function and left ventricular mass index by echocardiography and determined NT-proBNP blood levels. Patients were divided into two groups depending on the NT-proBNP concentration. The group 1 consisted of 64 (27,6%) patients with NT-proBNP >125 pg/ml, the group 2 — 168 (72,4%) patients with NT-proBNP 125 pg/ml, the most significant was the C/T genotype of MTHFR C677T polymorphism (rs1801133), 95% confidence interval (CI) for the odds ratio (OR) and relative risk (RR) of HF was 4,82 and 3,29, respectively (95% CI for OR=2,24-10,60; for OR=1,80-6,39). The A/G and G/G genotypes of the MTRR Ile22Met polymorphism (rs1801394) were statistically significant. The probability of HF with the A/G genotype of the MTRR gene increased by more than 2 times (OR=2,32, 95% CI=1,15-4,64), and the OR of its development was 1,77 (95% CI=1,11-2,69). The probability of HF with the G/G genotype increased more than 3 times (OR=3,65, 95% CI=1,37-9,76), and the OR of its development was 2,20 (95% CI=1,25-3,27). Correlation analysis revealed a direct relationship between the NTproBNP levels and polymorphism of the MTHFR (r=0,47; p 125 pg/ml depends on genetic determinism. Candidate genes for the HF in HTN patients with high adherence to treatment are the genotypes C/T of MTHFR C677T polymorphism (rs1801133), and A/G and G/G of MTRR Ile22Met polymorphism (rs1801394).

The polymorphisms of beta-adrenergic receptors genes and a risk of atrial fibrillation development in patients with a heart failure

Objective: to study the relationship of gene polymorphisms of the b-adrenoreception system with the risk of atrial fibrillation in patients with heart failure.Material and methods. 286 patients with heart failure on the background of post-infarction cardiosclerosis were included. Of these, 25 (8.7 %) patients had the atrial fibrillation. The genotyping was performed using 4 polymorphisms (Gly389Arg of the b1-adrenoreceptors gene, Ser49Gly of the b1-adrenoreceptors gene, Gln27Glu of the b2-adrenoreceptors gene and Ser275 of the b3-subunit of G-protein gene) using the polymerase chain reaction. The genetic and epidemiological analysis was carried out using the SNPStats program.Results. Patients with heart failure with the G / C genotype of Gly389Arg polymorphism of the b1-adrenoreceptors gene have a lower risk of developing atrial fibrillation (OR=0.14 (0.03–0.61), p=0.0043, co-dominant model of heredity).The data on a decrease in the risk of atrial fibrillation in patients with heart failure and with the G/C genotype Gly389Arg polymorphism of the b1-adrenoreceptors gene are also confirmed in the overdominant (OR=0.15 (0.03–0.64), p=0.0012), as well as in the dominant (OR=0.23 (0.08-0.69), p=0.0029) and the log-additive (OR=0.40 (0.17-0.94), p=0.019) models.Findings. The results allow us to conclude that congenital genetic differences in the pathways of b-adrenoreception can be associated with the development of atrial fibrillation in patients with heart failure

MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate.

Aim: To investigate the relationships of polymorphisms in genes whose protein products are related in the metabolic pathway of folic acid, particularly MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C, and disease activity in Mexican patients with rheumatoid arthritis (RA) treated with methotrexate (MTX).Materials and Methods: Sixty-eight patients with RA were included in the study who were being treated with MTX, either with or without other drugs. In addition to general data, disease activity was measured by the disease activity score 28 (DAS28). Single nucleotide polymorphisms (SNPs) genotyping was performed by allelic discrimination using real-time polymerase chain reaction.Results: Differences in genotype (homozygotic or heterozygotic for each allele), allele distributions, and phenotype were not statistically different between the RA group and control populations. We did not find any association between the studied polymorphisms and disease activity nor with the intragroup variables (e.g., clinical activity, body mass index, and single- or combined-drug treatment) or between genetic markers; we also did not find any association within the RA group or between the RA group and control populations.Conclusion: Additional studies of more polymorphisms related to this or other metabolic pathways are required to determine the influence of genetics on disease activity in RA.

Relationship of oestrogen receptor alpha gene polymorphisms with risk for benign prostatic hyperplasia and prostate cancer in Chinese men

The relationship of oestrogen receptor with benign prostatic hyperplasia (BPH) and prostate cancer (PC) is not clear at present. This study aimed to investigate the molecular mechanism underlying the occurrence and development of BPH and prostate.Two hundred forty-four PC cases, 260 BPH patients, and 222 healthy men were recruited from Han people in China, and the oestrogen receptor alpha (ESRα) gene polymorphism (rs2234693 [PvuII] and rs9340799 [XbaI]) on intron 1 was determined. The relationship of gene polymorphism with PC and BPH was evaluated with Logistic regression, and the linkage disequilibrium and haplotyping were assessed with SHEsis software.The risk for PC in BPH patients with PvuII C allele was higher (OR = 1.437, 95% CI: 1.110–1.859), but the differentiation degree of cancer cells was relatively better in PC patients with PvuII C allele (OR = 0.419, 95% CI: 0.285–0.616), and most of them are circumscribed (OR = 0.706, 95% CI: 0.485–1.02). There was significant linkage disequilibrium between PvuII and XbaI. The genotype TTAG not only induced BPH (OR = 6.260, 95% CI: 1.407–27.852), but increased the risk for PC (OR = 6.696, 95% CI: 1.504–29.801). However, the genotype TTAG in BPH patients had no relationship with the risk for PC (P > 0.05). Furthermore, men with haplotype TG were more likely to suffer PC (OR = 9.168, 95% CI: 2.393–35.119), but men with haplotype TA and enlarged prostate had a low risk for PC (OR = 0.708, 95% CI: 0.551–0.912).These results show the relationship between ESRα gene polymorphism and susceptibility to PC and BPH in Chinese men, and the ethnic and regional difference as well.

Association between clopidogrel resistance and polymorphism of platelet adenosine diphosphate receptor in patients with coronary atherosclerotic disease

To investigate the relation of clopidogrel resistance to polymorphism of adenosine diphosphate receptor (P2Y12). Three hundred and seventy patients with coronary atherosclerotic heart disease, who were admitted in hospital from May 2011 to November 2012 and underwent percutaneous coronary intervention, were enrolled in the study. All patients received antiplatelet therapy (oral aspirin 100 mg per night and clopidogrel 75 mg per day for >7 d). The gene polymorphisms of C34T and G52T P2Y12 receptor were detected by using DNA sequencing technique. The relationship of gene polymorphism with the incidence of clopidogrel resistance and clinical outcomes were analyzed. Among 370 patients, clopidogrel resistance developed in 100 cases, including 36 males (36%) and 64 females (64%). In the C34T locus, 212 cases were of CC genotype and 158 were of CT+TT genotype; the incidence of clopidogrel resistance in CC genotype was significantly lower than that in CT+TT genotype (P<0.05). In the G52T locus, 218 cases were of GG genotype and 152 cases were of GT+TT genotype; the incidence of clopidogrel resistance in GT+TT genotype were significantly higher than that in GG genotype (P<0.05). After 1-year follow-up, patients with CC genotype had lower incidence of angina recurrence than patients with CT+TT genotype did (13.2% vs 19.6%, Χ2=4.956, P<0.05), and patients with GG genotype had lower incidence of emergency revascularization, angina, and cardiovascular composite endpoint events than patients with GT+TT genotype did (Χ2=4.135,6.823,5.916, Ps<0.05). T-34, -52 mutations on P2Y12 receptor gene may be a risk factor for clopidogrel resistance and adverse cardiovascular events.