Polymorphism of ABO*O alleles and its clinical significance

Background. 62 ABO*O alleles of the ABO system are known. Some ABO*O alleles may be accompanied by the presence of residual A-glycosyltransferase activity in people of group O, which may lead to errors in determining the blood group. This confirms the important clinical significance of the ABO*O allele polymorphism. Knowledge of ABO*O gene polymorphisms and their prevalence contributes to the prevention of errors in determining the blood group of the ABO system.Objective: to study allele variants of the ABO*O gene in Russians.Materials and methods. The blood samples of 14,000 people were examined. The blood group was determined using anti-A, anti-Aweak, anti-B, lectin (anti-A1) and gel cards, as well as by cross-sectional method using standard red blood cells of O, A, and B groups. In one patient, the method of adsorption-elution with cold elution was used to identify a weak variant of antigen A, and the method of thermal elution was used to eliminate antigen- blocking plasma factors. Molecular determination of ABO*O alleles was performed in 130 individuals by polymerase chain reaction with sequence- specific primers and Sanger direct sequencing.Results. 13 allelic variants of the ABO*O gene were identified (10 with a typical deletion of c.261delG / N and 3 nondeletional alleles with polymorphism c.802G>A). Deletion alleles of ABO*O.01 were found in 92.85 % of the examined patients, nondeletion alleles of АВО*О.02 group – in 7.15 % of cases. The ABO*O.01.01 allele was detected with a frequency of 67.14 %, other deletion alleles – much less frequently: ABO*O.01.02 and ABO*O.01.11 – 5.71 %, ABO*O.01.26 – 5.00 %, ABO*O.01.12 – 4.30 %, ABO*O.01.13 and ABO*O.01.44 – 1.43 %, ABO*O.01.05, ABO*O.01.46, ABO*O.01.68 – 0.71 % each. Non-deletional alleles were found with the following frequencies: ABO*O.02.01 – 4.3 %, ABO*O.02.03 allele – 2.14 %, ABO*O.02.02 – 0.71 %. All individuals with the O group with the nondeletional allele had the Oαβ group, except for one patient (with the ABO*O.01.02 O.02.02 genotype), who had the Oβ group.Conclusion. For the first time, the immunogenetic characteristics of Russians are given according to ABO*O genes. Erythrocyte genomics helps to resolve the ambiguity of serological methods results and allows understanding mechanisms of different phenotypes formation. For the correct definition of natural isohemagglutinins and weak antigens variants should be used at least two different serological methods.

Study of the association of gene polymorphism with the risk of non-communicable diseases in martial artists

Objective: to study the effect of genetic polymorphisms: rs rs9939609 (FTO gene), rs4994 (ADRB3 gene), rs1042713 (ADRB2 gene), rs2228570 (VDR gene), rs1801133 (MTHFR gene) on anthropometric and lipid metabolism indicators in athletes representing martial arts.Materials and methods: studies of anthropometric and biochemical parameters, genetic polymorphisms were carried out in 120 athletes (101 men and 19 women) who are engaged in martial arts. Anthropometric studies were performed by measuring height (cm), body weight (kg), followed by calculating body mass index (BMI, kg / m2). Biochemical nutritional status markers were determined using the ABX Pentra 400 analyzer (HORIBA ABX SAS, France) in an automatic mode. Genotyping was performed using allele­specific amplification using TaqMan probes complementary to polymorphic DNA regions and real­time detection of the results using reagent kits from Syntol, Russia. Studies were performed on the device CFX96 Real Time System (Bio­Rad, USA). Statistical processing of the results was performed using the PASW Statistics 20 system.Results: as a result of generic Diovan athletes martial artists on the risk of non­communicable diseases, discovered that the frequency of allele A of rs9939609 polymorphism of the FTO gene they have is 43.9 %, allele polymorphism rs4994 ADRB3 gene — 10.9 %, G allele of rs1042713 ADRB2 gene polymorphism — 52.6 %, G allele of the polymorphism rs2228570 VDR gene with 44.9 % and allele t of rs1801133 in the MTHFR gene to 36.7 %. An association was found between the value of anthropometric indicators in male martial artists and the presence of polymorphisms rs9939609 (FTO), rs1042713 (ADRB2) and rs2228570 (VDR).Conclusions: the reason for the identified dyslipidemia in martial artists may be not only the previously detected violations of the structure of their nutrition, but also the presence of certain genetic polymorphisms, in particular, rs4994 of the ADRB3 gene and rs1042713 of the ADRB2 gene.

Comprehensive analysis of the 5-HTTLPR allelic polymorphism effect on behavioral and neurophysiological indicators of executive control in people from different ethnic groups in Siberia

The allelic polymorphism of the serotonin transporter’s gene 5-HTTLPR is considered as one of the factors determining an individual genetic predisposition to the development of a wide range of affective disorders, including depression. Many studies have shown that the climatic and social conditions of people’s life can have a significant impact on the connections of 5-HTTLPR with the risk of depression. The stop-signal paradigm (SSP) is an experimental method allowing evaluating an individual ability to the self-control of behavior in a changing environment. In the SSP experiment, a subject should either press one of several buttons quickly after the appearance of the target stimuli or suppress the already started movement if an inhibitory signal follows the target stimulus. The aim of this study is a research of associations between the allelic the 5-HTTLPR polymorphism and the individual scores of the personal anxiety level, as well as the behavioral and neurophysiological indicators of the ability to self-control over motor reactions in the SSP. The study was conducted among people from three ethno-regional groups: healthy Caucasoids from Novosibirsk, the Mongoloid groups of the indigenous population of the Tuva Republic and Sakha Republic (Yakutia). Genetic, ethnographic, and psychological influences on an individual’s ability to control motor responses were compared. The amplitude of the premotor peak of the evoked brain potential was used as a neurophysiological marker of the person’s readiness to the execution of target-directed activity. It was revealed that the frequency of the S-allele polymorphism 5-HTTLPR was significantly higher for both mongoloid groups compared to the Caucasoids. The S/S genotype was associated with an increased level of personal anxiety and at the same time with a better ability to the self-control of behavior in the SSP experiment. Anxiety level, participants’ sex, ethnicity, and allelic polymorphism 5-HTTLPR had a statistically significant effect on the amplitude of the premotor readiness potential recorded under the SSP conditions in the frontal and parietal-occipital cortical regions. Our data support the hypothesis that the S/S genotype of the 5-HTTLPR polymorphism may be associated with more success in adapting to the climatic conditions connected with high life risk in comparison to L/L and L/S genotypes.

Genotype Variations and Association between PAI-1 Promoter Region (4G/5G and -844G/A) and Susceptibility to Acute Myocardial Infarction and Chronic Stable Angina

The present study aimed at investigating the 4G/5G and -844G/A polymorphisms and plasma concentration of PAI-1 in patients with acute myocardial infarction (AMI) and chronic stable angina (CSA) in Indian population. It included 100 patients with AMI and stable angina and 100 healthy controls. All study subjects were typed for two PAI polymorphisms (4G/5G and -844G/A) through PCR-RFLP and level of PAI through ELISA. The comparison of AMI and CSA independently with control in terms of PAI-1 level was statistically significant but not between AMI and CSA. The frequency of 4G/4G and 4G/5G genotype and 4G allele was significantly higher in AMI cases than in control and was found to increase the risk of AMI. There was a significant relationship between 4G/5G polymorphism and AMI risk under the dominant and codominant genotype. The frequency of 4G/4G genotype and 4G allele was significantly higher in CSA cases than in control group and increases the risk of CSA. There was no significant association between 4G/5G polymorphism and CSA risk under recessive, dominant, and codominant models. The genotype and allelic frequencies difference between the cases (AMI and CSA) and control with regard to -844G/A polymorphisms were statistically nonsignificant. Also, we did not detect any significant association of -844G/A polymorphism with AMI and CSA in recessive, dominant, and codominant models. Along with the traditional risk factors, the 4G/5G allele polymorphism is an independent risk factor for the development of AMI. The detection of 4G/5G allele may therefore be helpful in primary prevention. Patients who carry the 4G/5G allele polymorphism have high concentrations of PAI-1, which might be involved in incidents leading to AMI. The present study for the first time revealed significant association of 4G/5G allele polymorphism with high risk of AMI in Indian population and will be helpful in identifying the genetic risk factors associated with AMI and CSA and for better management of diagnostic measures.

Genetic variability and biodiversity of Ukrainian Gray cattle by the BoLA-DRB3 gene

At the current stage of genetic studies of cattle, more and more attention is being drawn to autochthonous breeds. Native cattle have a number of prominent phenotypic traits and have preserved unique genes and their combinations lost by modern commercial breeds, which would be valuable to use in selective programs. We surveyed polymorphism of the Ukrainian autochthonous Gray breed according to alleles of exon 2 of the BoLA-DRB3 gene. The uniqueness of the gene lies in the broad variability of its allele variants. Significant informativeness at DNA level is quite important for genetic studies. We surveyed allele polymorphism using the PCR-RLFP method on DNA isolated from 88 samples of blood of cows and 5 samples of sperm. We identified 28 alleles, of which 23 variants were nomenclature ones and 5 (jba, *jab, *jbb, *nad and *nda) were “without established nomenclature”, their share accounting for 8.9%. Four alleles *06, *12, *16 and *jba had a frequency above 5% and occupied 69.9% of the breed’s allele fund overall. The commonest allele was BoLA-DRB3.2*16 (44.1%). In total, we found 40 genotypes. Considering the significant dominance of variant *16, as expected, 5 genotypes with its inclusion occurred: *16/*16, *12/*16, *06/*16, *16/*24 and *jba/*16. It was present in the genotype of two out three studied animals. Parameters of heterozygosity, effective number of alleles, Shannon and Pielou indices indicate that Ukrainian Gray cattle are characterized by lowest level of genetic variability and biodiversity according to the BoLA-DRB3 gene compared with other breeds. Due to significant dominance of allele *16, the breed has no inbred motifs. We noted deviation toward increase in homozygosity without deviations from the norm of the distribution according to Hardy-Weinberg equilibrium. The obtained results will be used for genetic-populational programs with the purpose of improving the genetic potential of cattle breeds in terms of economically beneficial traits and diseases of cattle.

COMPREHENSIVE ANALYSIS OF POLYMORPHIC VARIANTS OF GENES OF TNF-α AND ER1 IN PATIENTS WITH ATOPIC ASTHMA

Bronchial asthma (BA) is a multifactorial disease, genetic factors play an important role in its etiopathogenesis. At the same time, data on associations of polymorphic variants of the estrogen receptor gene with BA are quite contradictory. Objective of this research was to study the peculiarities of allele polymorphism frequencies of ER1 and TNF-α genes and their combinations in patients with atopic BA depending on the disease severity. Materials and methods: in the course of a retrospective single-center comparative pilot study by PCR/RFLP analysis, the frequencies of alleles and genotypes for the ER1 and TNF-α genes were determined in 78 prepubertal children (9 [6–13] years) with atopic BA. The population comparison group included 115 people. Results: the study revealed that in BA patients with moderate severity, genotypes Xx (48% and 14%; OR=6,067 CI=[1,653–22,268]), and Pp (94% and 47%, respectively; OR=18,074 CI=[2,319–140,854]) of the ER1 gene were statistically significantly more common than in the comparison group. A statistically significant difference was found in the distribution of genotype combinations for the XbaI and PvuII polymorphisms of the ER1 and –308A genes>G of TNF-α gene polymorphism in patients with BA and in the comparison group (2=31,761, p=0,0043). The frequency of the combined a-PpXx genotype in BA patients was higher than in the comparison group (22% and 3%, OR=11,09, p<0,0001). Conclusion: associations were found between the severity of BA and the genotype of the ER1 gene. The revealed absence of associations of polymorphism of the ER1 gene and BA with gender is probably due to the fact that we observed the direct influence of genetic factors without the influence of hormonal background.

Diet and PPARG2 Pro12Ala Polymorphism Interactions in Relation to Cancer Risk: A Systematic Review

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.

MiR-608 overexpression in idiopathic pulmonary fibrosis (IPF)

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology. Objective To test miR-608 expression and its targets in IPF patient samples. Methods RNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its’ rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism. Results miR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19–3.9]). Conclusion miR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.