Allele Frequencies Of Genes Research Articles

SLCO1B1 and ABCG2 Gene Polymorphisms in a Thai Population.

IntroductionGenetic polymorphisms of drug transporters influence drug transporter activity and alter pharmacokinetic profiles of the drugs. Organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) are important transporters encoded by solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene and ATP-binding cassette subfamily G member 2 (ABCG2) gene, respectively. Polymorphisms in these genes are associated with increased plasma statins concentrations, statin-induced myopathy and poor response to allopurinol treatment.PurposeWe explored allele and genotype frequencies of SLCO1B1 and ABCG2 genes including their predicted phenotypes in 53 Thai participants. Of these, 17 had chronic kidney disease and were on statins.Materials and MethodsGenotyping analysis for SLCO1B1 c.521T>C (rs4149056), c.388A>G (rs2306283), g.-11187G>A (rs4149015), and ABCG2 c.421C>A (rs2231142) was done by using TaqMan® Real time PCR. All were tested for Hardy–Weinberg Equilibrium.ResultsMost of the participants (80%) had normal function haplotypes SLCO1B1 (*1A and *1B) while decreased (*5, *15, and *17) and unknown (*21) function haplotypes were less observed. Four phenotypes of SLCO1B1 were observed: 69.81% had normal function (*1A/*1A,*1A/*1B, and *1B/*1B), 13.21% had intermediate function (*1A/*17, *1B/*15 and *1B/*17), 9.43% had indeterminate function (*1A/*21 and *1B/*21) and 7.55% had low function (*5/*15, *15/*15, and *15/*17). ABCG2 c.421A allele frequency was 25%. The frequency of ABCG2 c.421CA and AA phenotypes were 37.7% and 5.7%, respectively. The allele and genotype frequencies observed are consistent with reports in Asians. However, there were differences in major allele distributions between Asians and Caucasians for SLCO1B1 c.388A>G; SLCO1B1 c.388G were highly found in Asians, but c.388A were more observed in Caucasians.ConclusionThis study showed that in the Thai population, there were 4 SNPs of SLCO1B1 and ABCG2 genes. This finding may be clinically applied to minimize inter-individual variability of drugs such as statins and allopurinol. Further study with a larger sample size is needed to assess the drug profiles and responses to treatment.

The association study of WWP2 gene polymorphisms with delayed encephalopathy after acute carbon monoxide poisoning

Objective: To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods: From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ(2) test, and χ(2) test was used for association analysis. Results: For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group (P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups (P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion: It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Differential Gene Expression and Allele Frequency Changes Favour Adaptation of a Heterogeneous Yeast Population to Nitrogen-Limited Fermentations.

Alcoholic fermentation is fundamentally an adaptation process, in which the yeast Saccharomyces cerevisiae outperforms its competitors and takes over the fermentation process itself. Although wine yeast strains appear to be adapted to the stressful conditions of alcoholic fermentation, nitrogen limitations in grape must cause stuck or slow fermentations, generating significant economic losses for the wine industry. One way to discover the genetic bases that promote yeast adaptation to nitrogen-deficient environments are selection experiments, where a yeast population undergoes selection under conditions of nitrogen restriction for a number of generations, to then identify by sequencing the molecular characteristics that promote this adaptation. In this work, we carried out selection experiments in bioreactors imitating wine fermentation under nitrogen-limited fermentation conditions (SM60), using the heterogeneous SGRP-4X yeast population, to then sequence the transcriptome and the genome of the population at different time points of the selection process. The transcriptomic results showed an overexpression of genes from the NA strain (North American/YPS128), a wild, non-domesticated isolate. In addition, genome sequencing and allele frequency results allowed several QTLs to be mapped for adaptation to nitrogen-limited fermentation. Finally, we validated the ECM38 allele of NA strain as responsible for higher growth efficiency under nitrogen-limited conditions. Taken together, our results revealed a complex pattern of molecular signatures favouring adaptation of the yeast population to nitrogen-limited fermentations, including differential gene expression, allele frequency changes and loss of the mitochondrial genome. Finally, the results suggest that wild alleles from a non-domesticated isolate (NA) may have a relevant role in the adaptation to the assayed fermentation conditions, with the consequent potential of these alleles for the genetic improvement of wine yeast strains.

Effects of low-density urbanization on genetic structure in the Song Sparrow.

Urbanization fragments landscapes and can impede the movement of organisms through their environment, which can decrease population connectivity. Reduction in connectivity influences gene flow and allele frequencies, and can lead to a reduction in genetic diversity and the fixation of certain alleles, with potential negative effects for populations. Previous studies have detected effects of urbanization on genetic diversity and structure in terrestrial animals living in landscapes that vary in their degree of urbanization, even over very short distances. We investigated the effects of low-intensity urbanization on genetic diversity and genetic structure in Song Sparrows (Melospiza melodia). We captured 208 Song Sparrows at seven sites along a gradient of urbanization in and around Blacksburg, VA, USA, then genotyped them using a panel of fifteen polymorphic microsatellite loci. We found that genetic diversity was comparable among the seven study sites, and there was no evidence of genetic structuring among sites. These findings suggest that over a gradient of urbanization characterized by low density urban development, Song Sparrows likely exist in a single panmictic population.

ASSOCIATION BETWEEN DIABETICS AND INTESTINAL CANCER WITH THE RISK OF MUTATION IN CD38 GENE IN IRANIAN POPULATION.

Intestinal cancer often occurs in type 2 diabetic patients. The concept of increasing insulin levels and insulin-like growth factor in the blood with type 2 diabetes are stimulated with the growth and depletion of cloned cell walls, and the continuation of this process leads to the cellular deformation. This is the evidence for intestinal cancer in type 2 diabetes in population. In this study, we aimed to find out the relationship between diabetics and intestinal cancer based on CD38 gene mutation. Samples were collected from 200 population including normal and case ones. PCR products related to rs 6449181 of CD38 gene was amplified with ARMS-PCR technique, and a 420-bp sharp banding was observed as well. According three ARMS-PCR techniques, three primers were designed by oligo7 software. Primers include F1, F2 and R (amplifying for normal, mutant and reverse primer respectively). This band was observed using a primer F1 that carries the wild type nucleotide using a primer, and when it is used with the F2 primer, it brings the mutant primer to populations of patients with diabetes and diabetes-cancer. In addition, the clinical results including body mass index, blood glucose and insulin level were analyzed. The means ±SD and Tuckey's post hoc test were significant between the clinical characterization parameters between cases and healthy populations. The allelic gene frequencies and Hardy-Weinberg equilibrium between nucleotides were evaluated, and the significant level between the alleles and gene frequencies was observed. In general, the current study found that there is a relationship between diabetes and intestinal cancer among the studied populations.

Glutathione S-Transferase Theta 1 / Mu 1 Null Genotype and Risk of Development of Actinic Keratosis in Pakistani Population.

To assess the frequency and association of Glutathione S-Transferase Theta 1 and Glutathione S-Transferase Mu 1 null genotypes in development of actinic keratosis (AK) in a group of Pakistani population. Case-control analytical study. Department of Biochemistry, Islamic International Medical College, Rawalpindi in collaboration with Department of Dermatology, Railway Hospital and Rural Health Center, District Health Office, Rawalpindi from September 2018 to September 2019. Methodology: A total of 86 participants were included in this study with 27 biopsy proven cases of AK and 59 matched controls. Blood samples were collected after obtaining written informed consent; and DNA was extracted by Chelex™ method. Multiplex PCR (M-PCR) was done to find respective allelic frequencies of GSTM1 and GSTT1 genes in both cases and controls. Results: Mean age of participants in cases and controls was 62.93 ±10.29 years and was 61.42 ±9.96 years, respectively. There were 18 males (66.7%) and 9 females (33.3%); and 43 males (72.9%) and 16 females (27.1%) in cases and controls, respectively. There was a significant association of GSTT1 null genotype with AK (OR: 2.72, 95% CI: 1.05-7.05, p = 0.037). There was a positive correlation between GSTT1 null genotype and AK (r = 0.225, p = 0.037). GSTT1 null genotype has a significant association for AK development in the studied Pakistani population. Key Words: Actinic keratosis, Glutathione S-Transferase Mu 1, Glutathione S-Transferase Theta 1, Polymerase chain reaction, Squamous cell carcinoma.

DEVELOPMENT OF PRIMARY OPEN-ANGLE GLAUCOMA AND DELETION POLYMORPHISM OF THE GLUTATHIONE-S-TRANSFERASE GENES

The aim of the research. To investigate the association of the development of primary open-angle glaucoma with deletion polymorphism of glutathione-S-transferase genes. Materials and methods. Under our observation there were 172 patients, residents of Ukraine with primary open-angle glaucoma I–IV stages. Analysis of the deletion polymorphism of GSTM1 and GSTT1 genes was performed by real-time polymerase chain reaction using unified TaqMan Mutation Detection Assays Life-Technology (USA) test systems. Statistical analysis of the obtained data was performed using the MedStat package and the statistical package MedCalc v.15.1 (MedCalc Software bvba). Results and discussion. The detection of null alleles of the GSTM1 gene was observed in 39 % of patients in the control group, in patients with POAG a significant increase in the frequency of deletion polymorphism to 50–56 % was observed with the progression of the disease in stages II-IV. In patients with stage IV disease, the effect of the zero GSTM1- null allele on POAG course was determined (χ2=3.97; p=0.047), and the null allele of GSTM1 doubled the probability of developing the disease (OR=2.01; 95 % CI=1.01–4.01) in patients of group 4 compared with control. The null allele of the GSTT1 gene in the control group was found in 31 %, an increase in the frequency of the GSTT1-null allele was also observed in the second and fourth stages of POAG from 41 % to 54 %. Statistically significant differences of GSTT1 gene allele frequencies were determined between the control group and all patients with POAG (χ2=4.43; p=0.03), between the control and the 4th group (χ2=7.64; p=0.01), and between the 1st and 4th groups (χ2=5.52; p=0.02). An association with the development of POAG (χ2=4.43; p=0.03) was determined for the deletion polymorphism of the GSTT1 gene when comparing the control group with the data of all patients with POAG (1–4 groups). At stratification by stages of POAG (that is, by groups of patients), an association with the development of POAG was determined only in patients of group 4 (χ2=7.64; p=0.01) compared with the control group. Conclusions. The association of the null allele of the GSTT1 gene with POAG was established (p=0.03). The presence of the GSTT1-null allele significantly increased the risk of developing POAG (OR=1.75; BI=1.04–2.96) compared with the control group. The presence of null alleles (GSTM1-null and GSTT1-null) of the GST deletion polymorphism significantly increased the risk of stage IV POAG (OR=2.01; BI=1.01–4.01 and OR=2.66; VI=1.32–5.37, respectively) compared with the control group, which indicated the effect of zero alleles on the rapid progression of the disease.

Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias

AbstractThere is no standard or widely effective treatment of patients with moderate aplastic anemia (MAA) or hypo-productive uni-lineage cytopenias (UC). Eltrombopag (EPAG), a small molecule thrombopoietin mimetic, has previously been shown to result in durable multi-lineage hematologic responses with low toxicity in patients with refractory severe aplastic anemia (SAA). Its safety and efficacy in MAA are unknown. This prospective phase 2 study enrolled previously untreated and treated MAA and UC patients with clinically relevant cytopenias. EPAG was administered at doses escalating from 50 to 300 mg/d. Hematologic responses were assessed at 16 to 20 weeks. Responding patients were continued on EPAG until reaching defined robust or stable blood counts. EPAG was reinstituted for relapse. Thirty-four patients were enrolled between 2012 and 2017, including 31 with MAA and 3 with UC. Seventeen patients responded in at least 1 eligible lineage by the primary end point. A striking improvement in anemia was observed in a patient with Diamond-Blackfan anemia. EPAG was well tolerated, and it was discontinued for robust or stable blood counts in 12 of 17 patients after a median of 8 months. A majority required re-initiation of EPAG for declining counts, and all regained response. Two of 34 patients developed non–chromosome 7 bone marrow cytogenetic abnormalities while taking EPAG, without dysplasia or increased blasts. Somatic mutation allele frequencies in cancer genes did not increase overall on EPAG. EPAG is a well-tolerated oral treatment of cytopenias in patients with MAA/UC. This trial was registered at www.clinicaltrials.gov as #NCT01328587.

Allele frequencies of Bordetella pertussis virulence-associated genes identified from pediatric patients with severe respiratory infections

Bordetella pertussis (B. pertussis) infection occasionally causes severe respiratory infections in children. Potential association between virulence-associated gene alleles and severe clinical outcomes has been suggested; however, frequencies of these alleles in pediatric patients with severe pertussis have not been clarified.We retrospectively tested stored respiratory samples collected from B. pertussis-positive patients by polymerase chain reaction targeting for major virulence-associated genes; fimbrae (fim) serotype 3 (fim3), pertactin (prn), pertussis toxin A (ptxA), and pertussis toxin promotor (ptxP). Based on the identified sequences, multilocus sequence typing (MLST) was conducted. Association of gene allele frequency and clinical outcomes such as management in pediatric intensive care unit, intubation, and mortality was analyzed.Out of 25 patients with available samples, the most prevalent allele for each virulence-associated gene was fim3A (17/21, 83%), ptxA1 (20/23, 87%), prn2 (13/16, 81%), and ptxP3 (14/17, 82%). In the study, total of 3 MLST types were identified; MLST-1 from 3 patients (19%), MLST-2 from 10 patients (63%), and MLST-4 from 3 patients (19%). Detection rate of the major MLST type; MLST-2 was significantly higher for patients who required intubation compared to those who did not (6/6, 100% vs 4/10, 40%; p = 0.034).In conclusion, MLST-2 was the most common MLST type in B. pertussis isolated from Japanese children with severe pertussis. Further studies investigating its causal association with disease severity is warranted.

ALLELE FREQUENCY OF GLUTENIN SUBUNITS AND GLU-1 QUALITY SCORES IN SOME TURKISH BREAD WHEAT LANDRACES

There are eight centers of origin for cultivated plants and Turkey is located in the interception of two of these centers, the Near East and the Mediterranean. Therefore, Turkey is known to be the gene center for diversification and dispersion of such main cereal crops such as wheat, barley, rye and oat. This study was performed to determine glutenin gene allele frequencies and Glu-1 quality scores of 116 local wheat landraces of Turkish bread wheat. SDS-PAGE and PCR were used to identify glutenin gene alleles. The results showed that the studied Turkish local wheat landraces contained a total of 19 different subunits (3 subunits in Glu-A1, 11 in Glu-B1 and 5 in Glu-D1) with 50 different combinations. The highest and the lowest allelic combinations were determined in East Anatolia and the Aegean regions, respectively. Glu-A1c (65.11%), Glu-B1b (53.60%) and Glu-D1a (58.30%) were the most frequent alleles. The Glu-1 quality score was found to be 6.07 for the studied genotypes. Among the regions, the highest (7.18) and the lowest (4.80) mean Glu-1 scores were detected in Marmara and Southeastern Anatolia regions, respectively. 4 accessions (TR32846-6, TR36948-1, TR45105 and TR63536) were reported to have the highest Glu-1 quality score as 10. 6 genotypes (TR45398-4, TR48025-3, TR33264-6, TR393-5, TR52021-3 and TR45094) had the quality score of 9. Including more new landraces may contribute to discover new Glu-1 alleles.

TNF-α gene polymorphism in Iranian Azeri population

BackgroundTumor necrosis factor (TNF-α) is one of the major cytokines in the immune system that plays a major role in the inflammation in the body. The single nucleotide polymorphism (SNP) in the gene of this cytokine at position −308A/G that occurs in the promoter affects its expression level and subsequently predisposes to some malignancies and diseases. This study was conducted to investigate the TNF-α gene polymorphism at position −308A/G in the Azeri population. Material and methodsBlood samples were collected from 240 healthy and non-relevant Azeri individuals. After DNA extraction, the frequency of TNF-α gene genotypes and alleles at -308A/G was determined by allele specific-PCR method. Then comparisons between allele frequencies and TNF-α genotypes with other populations were performed using chi-square test and P value of <0.05 was considered significant. ResultsThe frequency percentage of GG, AG and AA genotypes in TNF-α cytokines at -308A/G in Azeri population was 70.8%, 26.7% and 2.5%, respectively. The frequency percentage of G and A alleles were 84.2% and 15.8%, respectively. The occurrence of TNF-α allele A at -308A/G is associated with high expression of this cytokine. ConclusionThe frequency of AA genotype was much lower than the other two genotypes, with low prevalence observed in other populations, which had a significant association with many diseases and even cancer; therefore, there was no significant difference with most studies examining the polymorphism of this cytokine in the same position.

SUN-312 INSIGHTS INTO THE ASSOCIATION OF CYP3A AND ABCB1 POLYMORPHISMS WITH TACROLIMUS-RELATED ADVERSE EFFECTS – VENTURING BEYOND THE CONVENTIONAL SNP-TAC LEVEL RELATIONSHIP

Tacrolimus (Tac), an immunosuppressant used in organ transplant recipients, exhibits an interindividual pharmacokinetic variability that affects the dose required to reach the target concentration in blood. Tac requires therapeutic monitoring of blood concentrations to prevent graft rejection owing to inadequate immunosuppression with low drug levels or toxicity due to high drug levels. Tac is metabolized by two enzymes of the cytochrome P450 family, CYP3A5 and CYP3A4, in the gut and liver, and transported in the gut by P-glycoprotein (P-gp), encoded by the MDR1/ABCB1 gene. The objective of the study is to investigate the association of CYP3A5, CYP3A4 and ABCB1 gene polymorphisms and their interactions with dose-adjusted Tac trough concentration in blood and drug-induced adverse effects in South Indian renal transplant recipients. Renal transplant recipients receiving Tac as an immunosuppressant were recruited from Government Medical College, Thiruvananthapuram, Kerala, India. Tac trough concentrations(C0), dose-adjusted Tac trough concentration(C0/D), doses, concomitant medications, drug adverse effects, etc. were recorded. DNA was isolated from blood collected from patients. SNP genotyping was performed using the PCR-RFLP method. Allele, genotype frequencies and linkage disequilibrium were calculated using UNPHASED software, v3.1.7. Comparison of C0/D to genotypes by one-way Anova and linear regression, box-plot analysis and multiple regression analysis to assess the effect of gene-gene interactions were performed using SPSS v20.0. The global variation in distribution of the polymorphisms was analyzed by comparing their allelic frequencies with existing world population data. CYP3A5*3 G (*3/*3) and CYP3A4*1G GG (wt/wt) genotypes were found to be strongly associated with higher Tac C0/D on post-operative day 6. CYP3A4*1B AA also showed a significant association with higher Tac C0/D. A combination of CYP3A5*3 GG and ABCB1 3435 CC genotypes could effectively predict a higher Tac C0/D in blood. We found that CYP3A5 AND CYP3A4 non-expressers had an increased chance of developing new-onset diabetes mellitus after transplantation (NODAT) compared to expressers. Carriers of at least one copy of ABCB1 G2677T Allele G were found to be at a higher risk of developing Tac toxicity. Allele frequencies of these gene polymorphisms in our population were found to be considerably different compared to other world populations. This is the first in-depth study including various functional polymorphisms and epistatic interactions between different genes to develop a robust prognostic and predictive pharmacogenomic biomarker with clinical applicability, which can predict individuals’ response to Tac. Our data will help identify patients who might have higher/lower Tac levels based on their genotype, and those at high risk of developing Tac-related complications can be identified before their organ transplant which can help the clinician decide the initial dosage of Tac. This tailor-made therapy could minimize adverse effects due to over-dosage and graft rejection due to low drug levels. Our findings on inter-ethnic differences in allele frequencies of drug metabolizer and transporter genes underscore the need to consider population-specific genetic backgrounds when conducting pharmacogenetic analyses and clinical trials.

Decimated little brown bats show potential for adaptive change

The degree to which species can rapidly adapt is key to survival in the face of climatic and other anthropogenic changes. For little brown bats (Myotis lucifugus), whose populations have experienced declines of over 90% because of the introduced fungal pathogen that causes white-nose syndrome (WNS), survival of the species may ultimately depend upon its capacity for adaptive change. Here, we present evidence of selectively driven change (adaptation), despite dramatic nonadaptive genomic shifts (genetic drift) associated with population declines. We compared the genetic makeups of wild survivors versus non-survivors of WNS, and found significant shifts in allele frequencies of genes associated with regulating arousal from hibernation (GABARB1), breakdown of fats (cGMP-PK1), and vocalizations (FOXP2). Changes at these genes are suggestive of evolutionary adaptation, given that WNS causes bats to arouse with unusual frequency from hibernation, contributing to premature depletion of fat reserves. However, whether these putatively adaptive shifts in allele frequencies translate into sufficient increases in survival for the species to rebound in the face of WNS is unknown.

Follicle –Stimulating Hormone Receptor Polymorphisms in Iraqi Women with Primary Amenorrhea

The study was carried to determine Single Nucleotide Polymorphism (rs6165) of Follicle Stimulating Hormone Receptor (FSHR) gene in blood samples of 62 Iraqi women with primary amenorrhea and 40 healthy control females. The research included chromosomal study and serum analysis of 62 patient samples. The samples were collected from Educational laboratories, City of Medicine, Baghdad and Biotechnology Dept. College of Science- Baghdad University through the period from October 2018 to March 2019. The determinations of SNP (rs6165) were carried out by real-time PCR. Results of rs6165 genotyping showed significant variations between PA patients and controls, Inspecting FSHR gene genotypes and allele frequencies in PA patients groups with the control group, revealed that there was significant variation in the heterozygous (AG) and homozygous mutant type(AA) genotype frequencies in (rs6165). the SNP of target gene may have a role in PA patients complaining from idiopathic puberty problems.

Single Nucleotide Polymorphism of Follicle Stimulating Hormone Receptor Gene in Iraqi Infertile Men

The study was directed to determine Single Nucleotide Polymorphism (rs6166 A&gt;G) of follicle stimulating hormone receptor gene and their association as a risk factor with male infertility in Iraqi sterile patient. In the present study after seminal and serum analysis 50 patient (25 Azoospermia and 25 oligozoospermia) and 50 healthy fertile control were joined. The samples were collected from the Biotechnology Department/college of science/Baghdad university and Kamal Al-Samarie IVF Hospital, Baghdad, Iraq. through the period of two months from November 2018 to January 2019. The SNP (rs 6166) determination was carried out by using real-time polymerase chain reaction (qPCR) of blood samples. The difference in the mean of genotype showed a significantly different (p&lt;0.05) in infertile patients group likened to corresponding means infertile control group. Survey of follicle stimulating hormone receptor gene SNP genotypes and allele frequencies in Azoospermia and oligozoospermia patient groups with the control group, showed that there was a significant variation in the heterozygous (AG) and homozygous mutant (GG) genotype frequencies in (rs 6166). It concluded that this SNP may have a role in an Azoospermia and oligozoospermia Iraqi patients complaining from idiopathic infertility.

Distribution of allele frequencies for genes associated with physical activity and/or physical capacity in a homogenous Norwegian cohort- a cross-sectional study

BackgroundThere are large individual differences in physical activity (PA) behavior as well as trainability of physical capacity. Heritability studies have shown that genes may have as much impact on exercise participation behavior as environmental factors. Genes that favor both trainability and participation may increase the levels of PA. The present study aimed to assess the allele frequencies in genes associated with PA and/or physical capacity, and to see if there is any association between these polymorphisms and self-reported PA levels in a cohort of middle-aged Norwegians of Scandinavian descent (n = 831; mean age mean age (± SD) 55.5 ± 3.8 years).ResultsThe genotype distributions of the ACTN3 R577X, ACE I/D and MAOA uVNTR polymorphisms were similar to other populations of European descent. When comparing the genotype distribution between the low/medium level PA group (LMPA) and high level PA groups (HPA), a significant difference in ACTN3 577X allele distribution was found. The X allele frequency was 10% lower in the HPA level group (P = 0.006). There were no differences in the genotype distribution of the ACE I/D or MAOA uVNTR polymorphism. Education and previous participation in sports or outdoor activities was positively associated with the self-reported PA levels (P ≤ 0.001).ConclusionsTo the best of our knowledge, this is the first study to report association between ACTN3 R577X genotype and PA level in middle-aged Scandinavians. Nevertheless, the contribution of a single polymorphism to a complex trait, like PA level, is likely small. Socioeconomic variables, as education and previous participation in sports or outdoor activities, are positively associated with the self-reported PA levels.

Polymorphism of lipid exchange genes in some populations of South and East Siberia

Lipid metabolism disorders underlie the pathogenesis of a number of diseases. Indigenous peoples of Siberia have a specific genetically determined type of metabolism supporting such lipid blood parameters that favor increased consumption (in comparison with Caucasians) of animal products. At the same time, indigenous Siberian ethnic groups are less susceptible to metabolic diseases. The objective of the presented study was to investigate the allele frequencies of lipid metabolism genes in indigenous populations of Siberia to identify the ethnic features of allele frequency distribution for polymorphic variants in genes CETP ( G1264A , rs5882), LPL ( C1791G , rs328) and FTO ( C83401A , rs8050136) in the samples taken from Buryats, Teleuts and Russians of Eastern Siberia, and to compare them with data on world populations. Samples of the Eastern ( N = 132) and Western ( N = 278) Buryats, Teleuts ( N = 120), Russians ( N = 122) and persons of mixed Buryat-Russian origin ( N = 56) were genotyped by real-time PCR using competitive TaqMan-probes. The obtained results have for the first time demonstrated that the CETP and FTO allele frequencies in the Buryat samples are intermediate between European and East Asian populations. Significantly lower incidence of the obesity-assossiated 83401A allele of the FTO gene has been shown in Buryats, compared with Russians, which is consistent with lower susceptibility of the indigenous ethnic groups to metabolic disorders. There have been no population differences in the distribution of LPL gene polymorphic variants associated with dyslipidemia, which means they probably do not contribute to the ethnic characteristics of the lipid profile. The intermediate frequencies of the CETP 1264G and FTO 83401A alleles found in the metis group demonstrate that the metabolic disorders associated with these variants can be rather expected in the descendants of mixed marriages than among Buryats. It has also been demonstrated that Teleuts differ by FTO 83401A allele frequency from some of the European groups and have the lowest detected frequency of the allele CETP 1264G associated with the favorable lipid blood parameters.

Climate change and the genetics of insecticide resistance.

Changes in global temperature and humidity as a result of climate change are producing rapid evolutionary changes in many animal species, including agricultural pests and disease vectors, leading to changes in allele frequencies of genes involved in thermotolerance and desiccation resistance. As some of these genes have pleiotropic effects on insecticide resistance, climate change is likely to affect insecticide resistance in the field. In this review, we discuss how the interactions between adaptation to climate change and resistance to insecticides can affect insecticide resistance in the field using examples in phytophagous and hematophagous pest insects, focusing on the effects of increased temperature and increased aridity. We then use detailed genetic and mechanistic studies in the model insect, Drosophila melanogaster, to explain the mechanisms underlying this phenomenon. We suggest that tradeoffs or facilitation between adaptation to climate change and resistance to insecticides can alter insecticide resistance allele frequencies in the field. The dynamics of these interactions will need to be considered when managing agricultural pests and disease vectors in a changing climate. © 2019 Society of Chemical Industry.

Vitamin D receptor and binding protein polymorphisms in women with polycystic ovary syndrome: a case control study

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, characterized by hyperandrogenism, oligomenorrhea, polycystic ovary morphology, and insulin resistance. Vitamin D deficiency and vitamin D receptor (VDR)/vitamin D binding protein (VDBP) gene variants could play an important role in susceptibility to PCOS and contribute to metabolic disturbances and menstrual dysfunction. We aimed to investigate the associations of VDR gene and VDBP gene polymorphisms with PCOS susceptibility and to elucidate the impacts of these polymorphisms on the hormonal and metabolic parameters of PCOS.MethodsWe recruited 432 women with PCOS and 927 controls. Polymorphisms in the VDR gene (VDR Fok-I, Cdx2, Apa-I, and Bsm-I) and VDBP gene (VDBP rs4588, rs7041, and rs22822679) were genotyped. A 75-g oral glucose tolerance test was performed.ResultsThe distributions of genotypes and allele frequencies in VDR and VDBP genes did not differ between PCOS and control. In women with PCOS, compared to the VDR Fok-I GG genotype, the VDR Fok-I AG genotype was significantly associated with increased levels of total testosterone (β = 5.537, P = 0.005). Compared to the VDR Cdx2 AC genotype, the VDR Cdx2 CC genotype was associated with increased levels of fasting insulin and HOMA-IR in women with PCOS, however, the associations were not statistically significant.ConclusionsThis finding indicates that genetic variations in VDR and VDBP were not associated with increased risk for PCOS. In contrast, the VDR Fok-I polymorphism was associated with testosterone level and the Cdx2 polymorphism with insulin sensitivity in PCOS. However, the Cdx2 polymorphism was not significantly associated with increased insulin and insulin sensitivity in women with PCOS after multiple linear regression.

Vitamin D receptor and collagen type1α1 gene polymorphisms in patients with postmenauposal osteoporosis

Purpose: The iam of this study was to investigate the genotype and allele frequencies of osteoporosis related candidate genes, VDR and COL1A1 and their relationship between biochemical and anatomic parameters in patients with postmenopausal osteoporosis and healthy women in the Cukurova region of Turkey.Materials and Methods: Eighty-four postmenopausal osteoporotic patients and fourty-five controls were recruited after obtaining informed consent. Four polymorphic restriction sites (ApaI, TaqI, BsmI and FokI) for the VDR gene and two polymorphic restriction sites (Sp1 and -1997G/T) for the COL1A1 gene were examined. All subjects were genotyped employing polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP).Results: The frequencies of VDR and COL1A1 polymorphism genotypes, alleles and haplotypes were not statistically significant between patients and controls. The VDR gene BsmI, ApaI and TaqI polymorphisms, and the COL1A1 -1997G/T and Sp1 polymorphisms had a strong linkage disequilibrium. The most common haplotypes were “BAt” for patients and “baT” for controls in the VDR gene, the “TG” haplotype (also “TS”) was the most common in two groups for COL1A1 gene.Conclusion: The VDR and COL1A1 gene polymorphisms play key roles in osteoporosis susceptibility and BMD in postmenopausal women. Our findings may imply that polymorphisms of the VDR and COL1A1 genes were not associated with low BMD or fractures in postmenopausal Turkish women.