BDKRB2 Genes Research Articles

Kinin Receptors and Kinin-Related Gene Expression in Astrocytic Brain Tumors.

Kinins are a set of peptides present in tissues that are involved in the inflammatory response and cancer progression. However, studies showing the expression of kinin receptors in human glioma samples are still incomplete and contradictory. The aim of the present study was to ascertain the expression of BDKRB1 and BDKRB2 genes, as well as the level of B1R and B2R proteins in human gliomas, depending on the degree of malignancy. Additionally, representative kinin-dependent genes with altered expression were indicated. The expression profile of kinin-dependent genes was determined using oligonucleotide microarray technique. In addition, RT-qPCR was used to assess the expression level of selected differentiating genes. The location of kinin receptors in brain gliomas was assessed using immunohistochemical methods. The oligonucleotide microarray method was used to identify 12 mRNA IDs of kinin-related genes whose expression was upregulated or downregulated in gliomas of different grades. In immunohistochemically stained samples, the concentrations of BR1 and BR2 proteins, measured by optical density, were statistically significantly higher in grade G3 vs. G2 and G4 vs. G3. Increased expression of kinin receptors BDKRB1 and BDKRB2 in brain gliomas, depending on the degree of malignancy, suggests the involvement of kinins and their receptors in the disease's pathogenesis. Quantitative assessment of mRNA BDKRB1, PRKAR1A, MAP2K, and EGFR in patients with brain tumors may hold diagnostic and therapeutic significance.

Genetic Biomarkers of Cardiovascular and Cerebrovascular Reserves in Athletes

As the practice of modern elite sports shows, the functional capabilities of the athlete's body have almost reached their limit. Further increase in the volume and intensity of physical activity is associated with the risk of desadaptative changes in the athlete's body. It is known that in endurance sports, the cardiovascular system is the main limiting factor in achieving a high athletic result. In this regard, a promising approach is to search for molecular genetic markers associated with high functional reserve of the cardiovascular system of athletes. A personalized approach in sports practice is an effective tool for sports selection, development of personalized training pro-grams to optimize the health status and achieve high performance of an athlete, as well as for the prevention of sports traumatism. (1) Background: to conduct a systematic review of the studies of candidate genes and their single-nucleotide variants (SNVs) associated with the functioning of the cardiovascular system in cyclical sports athletes.(2) Methods: A search for publications between 2000 - 2021 in the databases SCOPUS, Web of Science, Google Scholar, PubMed, e-LIBRARY, using the key words and their combinations; (3) Conclusions: the Identification of genetic markers (SNVs and polymorphisms of the ACE, BDKRB2, CMA1B, NOS3 and VEGFA genes) associated with the functional reserve of the cardiovascular system, can help cardiologists, sports physicians and trainers in developing personalized strategies for the selection of children / teenagers and the choice of sports specializations. Such a personalized approach will increase sports performance and reduce the risk of overtraining and failure to adapt during a difficult competitive period.

Genetic characteristics of competitive swimmers: a review.

A successful swimming performance is a multi-factorial accomplishment, resulting from a complex interaction of physical, biomechanical, physiological and psychological factors, all of which are strongly affected by the special medium of water as well as by genetic factors. The nature of competitive swimming is unique, as most of the competitive events last less than four minutes. Yet training regimens have an endurance nature (many hours and many kilometres of swimming every day), which makes it impossible to classify swimming by definitions of aerobic-type or anaerobic-type events, as in track and field sports. Therefore, genetic variants associated with swimming performance are not necessarily related to metabolic pathways, but rather to blood lactate transport (MCT1), muscle functioning (IGF1 axis), muscle damage (IL6) and others. The current paper reviews the main findings on the leading 12 genetic polymorphisms (located in the ACE, ACTN3, AMPD1, BDKRB2, IGF1, IL6, MCT1, MSTN, NOS3, PPARA, PPARGC1A, and VEGFR2 genes) related to swimming performance, while taking into consideration the unique environment of this sport.

The Bdkrb2 gene family provides a novel view of viviparity adaptation in Sebastes schlegelii

BackgroundBlack rockfish (Sebastes schlegelii) is a viviparous teleost. We proposed that the rockfish ovarian wall had a similar function to the uterus of mammals previously. In the present study, the well-developed vascular system was observed in the ovarian wall and the exterior surface of the egg membrane. In gestation, adaptation of the ovary vasculature to the rising needs of the embryos occurs through both vasodilation and neovascularization. Bdkrb2, encoding a receptor for bradykinin, plays a critical role in the control of vasodilatation by regulating nitric oxide production.ResultsEight Bdkrb2 genes were identified in the black rockfish genome. These genes were located on chromosome 14, which are arranged in a tandem array, forming a gene cluster spanning 50 kb. Protein structure prediction, phylogenetic analysis, and transcriptome analysis showed that eight Bdkrb2 genes evolved two kinds of protein structure and three types of tissue expression pattern. Overexpression of two Bdkrb2 genes in zebrafish indicated a role of them in blood vessel formation or remodeling, which is an important procedure for the viviparous rockfish getting prepared for fertilization and embryos implantation.ConclusionsOur study characterizes eight Bdrkb2 genes in the black rockfish, which may contribute to preparation for fertilization and embryo implantation. This research provides a novel view of viviparity adaptation and lays the groundwork for future research into vascular regulation of ovarian tissue in the breeding cycle in black rockfish.

Diet-gene interaction: effects of polymorphisms in the ACE, AGT and BDKRB2 genes and the consumption of sodium, potassium, calcium, and magnesium on blood pressure of normotensive adult individuals.

Functional variants in genes of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems have already been implicated in blood pressure (BP) modulation, but few studies have focused on a nutrigenetics approach. Thus, the aim of this study is to verify the effects of the interaction between genetic polymorphisms (rs4340-ACE, rs699-AGT, and rs1799722-BDKRB2) and micronutrient consumption (sodium, potassium, calcium, and magnesium) on BP values of normotensive adult individuals. The study included 335 adults, men and women, 25.5 (6.6) years old. Biochemical, anthropometric, BP measurements, and food intake data were assessed for all participants. Gene-nutrient interaction on BP outcome was tested by multiple linear regression with manual backward stepwise modeling. Our results indicated that individuals with G allele for rs699 polymorphism, in the increase of sodium and magnesium consumption, both in the genotypic model (sodium, p = 0.035; magnesium, p = 0.016) and in the dominant model (sodium, p = 0.009; magnesium, p = 0.006) had higher systolic BP (SBP) levels compared to AA homozygotes (sodium, p = 0.001; magnesium, p < 0.001). Also, individuals with the T allele for the rs1799722 polymorphism, with higher calcium intake, had significantly higher levels of SBP and diastolic BP (DBP) when compared to CC homozygotes (p = 0.037). In conclusion, our findings pointed for significant interactions between genetic polymorphisms (rs699-AGT and rs1799722-BDKRB2) and the consumption of micronutrients (sodium, magnesium, and calcium) on the BP variation. These findings contribute to the understanding of the complex mechanisms involved in BP regulation, which probable include several gene-nutrition interactions.

The regulatory role of exosomal CagA and microRNAs derived from H. pylori-related gastric cancer cells on signaling pathways related to cancer development: a bioinformatics aspect

Exosomes are small vesicles outside the membrane, which are secreted by healthy, cancerous, and bacterial infected cells. These worthy vesicles carry shared information between adjacent cells and cause cell-cell communication. Bacteria can also secrete vesicles similar to exosomes called outer membrane vesicles (OMVs). The OMVs, also called quasi-exosomes due to its similarity to exosomes, are bacterial extracellular membrane vesicles that are secreted to enhance the pathogenicity of the bacteria. The continued secretion of exosome by cells and quasi-exosome by bacteria in gastric cancer played a vital role in cancer progression to metastasis and acute cancer state. In gastric cancer associated with Helicobacter pylori infection, both cancerous and immune cells secretion are involved. Exosomes and quasi-exosomes interact with each other to overcome cancer or worsen it. Cancer cells, through the involvement of T lymphocytes and macrophages, make these cells to secrete. Exosomes stimulate the immune system and improve gastric cancer. Exosomes containing CagA, miR155, MET, and GGT factors play an important role in gastric cancer. The regulatory role of some of these factors such as microRNAs and CagA are evaluated by enrichment analysis. KEGG pathway analysis illustrated the most significant pathway of upregulated gene in gastric cancer patient with inflammation history of H. pylori. Functional annotation analysis of H. pylori-related gastric sample highlighted the cluster of genes which regulated signal transduction and cellular respond to stimulus mechanism. Also, the protein-protein interaction (PPI) network of upregulated genes manifest CXCL8, CDC42, and BDKRB2 genes as a core network. Regarding the augmentation role of candidate genes in metastasis, migration, and angiogenesis in gastric cancer and also their regulatory role in pathogenesis and expansion of H. pylori, these genes offer the therapeutic opportunity against H. pylori and gastric cancer parallelly. Our final analysis was based on microRNAs related database underline mir-499, mir-208a-3p, and mir-208b which are the most downregulated microRNAs in H. pylori-related gastric cancer and could serve as an anti-cancer therapeutic agent.

Genetic Determinants of Cardiovascular Reactions in Humans with Different Combinations of Alleles in NOs, ADRB2, BDKRB2 and ACE Genes in Response to the Diving Reflex

The diving reflex (DR) is a set of signaling interconnected reflex respiratory and cardiovascular reactions aimed at quickly adapting to diving, or otherwise, to hypoxia. This effect is achieved through reflexive deceleration of the heart’s rhythm, constriction of peripheral vessels and selective redistribution of blood to those organs which are most vulnerable to hypoxia (the brain and heart). Specificity of DR manifestations is determined by species affiliation among animals. The effectiveness of DR in humans depends on the nature of vegetative and humoral regulation in the cardiovascular system. The aim of this study is to determine whether protective cardiovascular mechanisms when diving vary in people with different polymorphisms genes, which produce factors are involved in the regulation of peripheral vascular tone (NOs, ADRB2, BDKRB2, ACE).96 volunteers (students; aged 18–24) were examined. These subjects were not adapted to diving. DR was activated by submerging their faces in cold water (12–14°C) under laboratory conditions. ECG records were taken for the resting state, during diving simulation (DS) and after apnea. The blood supply to peripheral vessels was measured indirectly using the pulse wave amplitude (PWA) of the photoplethysmogram (PPG). Vascular tone was calculated from the time of its spread (the pulse transit time, PTT). Blood pressure was recorded. DNA samples from all patients’ blood were isolated using phenol‐chloroform extraction. I/D polymorphism (rs4340) of the ACE gene was analysed using PCR. The results were analysed using Mann‐Whitney nonparametric tests (paired comparisons).According to the results of the study, significant decrease in PWA was found in subjects with C/C (ADRB2; n=56) and 4b4b (NOs; n=45) polymorphisms during DS (p&lt;0.01). In its turn, decline in PWA was less significant in subjects with A/A (ADRB2; n=36), G/G (ADRB2; n=21) alleles (p&lt;0.05). And in subjects with 4b4a (NOs; n=21), 4a4a (NOs; n=3) polymorphisms, PWA decreased is not significant. We suggests that the protective mechanisms in subjects with C/C (ADRB2) and 4b4b (NOs) polymorphisms are better expressed. According to the results of the ACE polymorphism study, significant differences in PTT were found between I/D (n=27) and I/I (n=23) alleles, as well as between with I/I and D/D (n=21) alleles at the control level (CL) and during DS (p&lt;0.01; p&lt;0.05). When BDKRB2 alleles were studied, significant differences in PWA between T/C (n=35) and C/C (n=24) alleles, as well as between T/T (n=13) and C/C alleles were found in all dives and during recovery (p&lt;0.01). In subjects with I/D, T/C (BDKRB2), C/C (ADRB2) and 4b4b polymorphisms, PWA increased in the recovery process when compared with CL (p&lt;0.01). This reflects an increase in blood volume in the peripheral vessels and indicates oxygen debt formed during DS.When diving was simulated, constriction of peripheral vessels was observed in all subjects examined, but its severity had significant individual differences. Studies have shown that the most effective defence mechanisms against hypoxia are those which develop when diving in people with I/D (ACE), T/C (BDKRB2), C/C (ADRB2) и 4b4b (NOs) polymorphisms.

Ассоциация полиморфизмов генов АСЕ, СМА1 и BDKRB2 с состоянием кислородтранспортной системы организма у юношей с разным уровнем двигательной активности

Ассоциация полиморфизмов генов АСЕ, СМА1 и BDKRB2 с состоянием кислородтранспортной системы организма у юношей с разным уровнем двигательной активности

Genetic effects of BDKRB2 and KNG1 on deep venous thrombosis after orthopedic surgery and the potential mediator

Deep venous thrombosis (DVT) is a common complication of orthopedic surgery. Genetic risk factors and high heritability carried a substantial risk of DVT. In this study, we aimed to investigate the potential association in the Han Chinese population between the polymorphisms of BDKRB2 and KNG1 and DVT after orthopedic surgery (DVTAOS). A total of 3,010 study subjects comprising 892 DVT cases and 2,118 controls were included in the study, and 39 single nucleotide polymorphisms (SNPs) in total (30 for BDKRB2 and 9 for KNG1) were chosen for genotyping. Two SNPs, rs710446 (OR = 1.27, P = 0.00016) and rs2069588 (OR = 1.29, P = 0.00056), were identified as significantly associated with DVTAOS. After adjusting for BMI, the significance of rs2069588 decreased (P = 0.0013). Haplotype analyses showed that an LD block containing rs2069588 significantly correlated with the DVTAOS risk. Moreover, bioinformatics analysis indicated that hsa-miR-758-5p and BDKRB2 formed miRNA/SNP target duplexes if the rs2069588 allele was in the T form, suggesting that rs2069588 may alter BDKRB2 expression by affecting hsa-miR-758-5p/single-nucleotide polymorphism target duplexes. Our results demonstrate additional evidence supporting that there is an important role for the KNG1 and BDKRB2 genes in the increased susceptibility of DVTAOS.

Association of the bradykinin receptors genes variants with hypertension: a case–control study and meta-analysis

Background: The present study was to investigate the role of bradykinin receptors genes polymorphisms on hypertension risk in Northern Han Chinese population. We also carried out a meta-analysis on Chinese to derive a more full assessment of this association. Methods and results: A total of 976 subjects from Northern Han Chinese and 7 studies with 1599 cases and 1425 controls were included in this case–control study and in the current meta-analysis, respectively. For the case–control study, we identified the genotypes of −58T/C and 1098A/G polymorphism in BDKRB2 and BDKRB1 genes, respectively, by TaqMan PCR method. Overall, we found significant association between the −58T/C polymorphism and the increased risk of hypertension in the allele comparison (p = 0.01, OR = 1.386, 95%CI [1.138–1.688]). Subgroup analysis by gender suggested that this obvious association could still be found in males, but not in females. For the 1098A/G polymorphism, no significant association was revealed in overall and subgroup analysis. For the meta-analysis involving the −58T/C polymorphism, a significant association between this polymorphism and hypertension was observed in the whole group. In Chinese Han subgroup, we found significant association with hypertension in allele comparison(C vs. T: p = 0.03, OR = 1.28, 95%CI 1.03–1.59, pheterogeneity = 0.05). Conclusions: Our case–control study indicated that −58T/C might be significantly associated with the increased risk of hypertension in Northern Han Chinese population, which was partially confirmed by our meta-analysis.

&amp;lt;i&amp;gt;ADRB2&amp;lt;/i&amp;gt;, &amp;lt;i&amp;gt;ADRB3&amp;lt;/i&amp;gt;, &amp;lt;i&amp;gt;BDKRB2&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;MTNR1B&amp;lt;/i&amp;gt; Genes Related to Body fat Modulation and Its Interaction with Physical Activity and Blood Pressure

Hypertension (HTN) is the risk factor that most contributes to mortality rates in the world, followed by physical inactivity and obesity. Despite the influence of genetic factors on the genesis of HTN, blood pressure levels are strongly influenced by environmental factors such as physical inactivity and overweight, characterizing it as a polygenic disease. Genetic components and environmental factors such as physical exercise may modulate the phenotype of individuals predisposed to medical conditions such as HTN, independently of modifiable factors such as increased levels of adiposity; however, studies have shown that polymorphic forms detected in genes involved in the mechanisms of blood pressure regulation and also related to body fat modulation may interact with physical activity levels and HTN. The aim of this article is to review the interactions between polymorphisms in ADRB2, ADRB3, BDKRB2 and MTNR1B genes, physical activity and blood pressure.

SNP-by-fitness and SNP-by-BMI interactions from seven candidate genes and incident hypertension after 20 years of follow-up: the CARDIA Fitness Study

The association of SNPs from seven candidate genes, including genotype-by-baseline fitness and genotype-by-baseline body mass index (BMI) interactions, with incident hypertension over 20 years was investigated in 2663 participants (1301 blacks, 1362 whites) of the Coronary Artery Risk Development in Young Adults Study (CARDIA) Study. Baseline cardiorespiratory fitness was determined from duration of a modified Balke treadmill test. A total of 98 SNPs in blacks and 89 SNPs in whites from seven candidate genes were genotyped. Participants that became hypertensive (295 blacks and 146 whites) had significantly higher blood pressure and BMI (both races), and lower fitness (blacks only) at baseline than those who remained normotensive. Markers at the PPARGC1A and BDKRB2 genes were nominally associated with greater risk of hypertension, while one marker each at the BDKRB2 and NOS3 genes were nominally associated with lower risk. The association of baseline fitness with risk of hypertension was nominally modified by genotype at markers within the ACE, AGT, BDKRB2, and NOS3 genes in blacks and the BDKRB2, EDN1, and PPARGC1A genes in whites. BDKRB2 rs4900318 showed nominal interactions with baseline fitness on the risk of hypertension in both races. The association of baseline BMI with risk of hypertension was nominally modified by GNB3 rs2301339 genotype in whites. None of the above associations were statistically significant after correcting for multiple testing. We found that SNPs in these candidate genes did not modify the association between baseline fitness or BMI and risk of hypertension in CARDIA participants.

Dipsogenic genes associated with weight changes during Ironman Triathlons

Thirst is regulated by a complex interaction of signalling pathways within the central nervous system, including components of the renin-angiotensin and kalikrein kinin systems, as well as the serotonergic pathways. The aim of this study was to determine whether there were any associations between polymorphisms within the ACE, BDKRB2, NOS3 and/or 5-HTT genes with weight changes during the 2000 and 2001 226 km South African Ironman Triathlons. Pre- and post-race serum [Na(+)] and body weights, as well as genotype data, were collected from 428 (61.1%) Caucasian male triathletes who were divided into three groups according to their relative weight loss during the triathlon (0-3, 3-5 and >5%). There was a significant linear trend for the distribution of both the BDKRB2 +9/+9 genotype and the 5-HTT SS genotype between the three weight loss groups, with the >5% group having the highest percentage of athletes with the +9/+9 genotype (chi(2)=5.3, P=0.021) and the highest percentage of athletes with the SS genotype (chi(2)=5.8, P=0.016). Likewise, the >5% group had the highest percentage of athletes with the combined SS 5-HTT and/or +9/+9 BDKRB2 genotypes (chi(2)=7.4, P=0.007). In conclusion, the functional SS genotype of the serotonin transporter-linked polymorphic region (5-HTTLPR) within the 5-HTT gene and the functional +9/+9 genotype of the BDKBR2 gene were associated with larger weight losses during the Ironman Triathlons. These findings suggest the involvement of the serotonergic pathways in the control of thirst and drinking behaviour and provide further evidence for the dipsogenic effect of circulating bradykinin.

The bradykinin β2 receptor (BDKRB2) and endothelial nitric oxide synthase 3 (NOS3) genes and endurance performance during Ironman Triathlons

We have previously shown that the insertion allele of the angiotensin-converting enzyme (ACE) gene was over-represented in the fastest South-African-born finishers of the South African Ironman Triathlons. As ACE is a component of the skeletal muscle kallikrein-kinin system (KKS), the aim of this study is to determine if there are any further associations between polymorphisms within the BDKRB2 and NOS3 genes, which encode for the KKS components, bradykinin beta(2) receptor and nitric oxide synthase, respectively, and ultra-endurance performance during the Ironman Triathlons. Four-hundred and forty-three male Caucasian triathletes who completed the 2000 and/or 2001 South African Ironman Triathlons and 203 healthy Caucasian male control subjects were genotyped for the functional -9/+9 polymorphism within exon 1 of the BDKRB2 gene and the G894T NOS3 gene polymorphisms. The BDKRB2 -9/-9 genotype occurred at a significantly higher frequency when the triathlete group (27.0%) was compared with the control group (19.3%, P=0.035). When divided into tertiles, there was also a significant linear trend for the NOS3 GG genotype distribution among the fastest (35.0%), middle (40.4%) and slowest (46.9%) finishers (P=0.039). The overall finishing times of the triathletes with an NOS3 GG genotype together with a BDKRB2 +9 allele were significantly slower than those with other genotype combinations (P=0.001). The NOS3/BDKRB2 genotype (beta=-0.150, B=-31.48, P=0.002), together with body mass index and age, accounted for 14.6% of the variance in the overall race time for the triathlon. In conclusion, both the NOS3 and BDKRB2 genes are associated with the actual performance during the Ironman Triathlons.