Genotype Frequencies Research Articles

Association Between the Risk of Dental Caries and DLX3 Gene Polymorphisms in Chinese Children.

To explore the association between the risk of dental caries and distal-less homeobox 3 (DLX3) gene in Chinese children. Based on the decayed, missing, and filled teeth (dmft) score, the children were divided into a control group (dmft = 0) and a case group (dmft ≥ 1). DLX3 gene (rs11656951 and rs2278163) polymorphisms were genotyped by polymerase chain reaction (PCR) and Sanger sequencing methods. Possible association of DLX3 gene (rs11656951 and rs2278163) polymorphisms with dental caries risk was assessed using the chi-squared test. Subgroup analysis of association was assessed by logistic regression analysis for the potential risk factors. The age at which toothbrushing was started, the brushing frequency, brushing with fluoride toothpaste, and regular dental visits were statistically significantly different between case and control groups (p 0.05). The frequencies of rs11656951 TT genotype and T allele were statistically significantly higher in the control group than in the case group. The chi-squared test showed that CT genotype (p = 0.026, OR = 0.613, 95%CI = 0.398-0.944) and TT genotype (p = 0.001, OR = 0.378, 95%CI = 0.212-0.673) were negatively correlated with caries susceptibility. The T allele of rs11656951 was more frequently discovered in the control group, and was statistically significantly associated with decreased caries susceptibility (p = 0.001, OR = 0.636, 95%CI = 0.486-0.831). The G allele of rs2278163 was obviously correlated with elevated caries susceptibility (p = 0.049, OR = 1.314, 95%CI = 1.000-1.725). DLX3 gene rs11656951 TT genotype was a protective factor for caries susceptibility in the subgroups gender, sweets intake, eating before sleep, brushing frequency, brushing with fluoride toothpaste, and dental visits. The GG genotype of rs2278163 was a risk factor for caries in subgroups eating before sleep, brushing without fluoride toothpaste, and regular dental. The TT genotype of rs11656951 was dramatically correlated with reduced caries risk in low (p = 0.004, OR = 0.387, 95%CI = 0.202-0.742) and moderate/high (p = 0.016, OR = 0.360, 95%CI = 0.154-0.840) groups. DLX3 gene rs11656951 TT genotype is a protective factor and rs2278163 GG genotype is a risk factor for caries susceptibility, especially in low and moderate/high subgroups.

Polymorphism Of Orosomucoid-Like 3 ORMDL3 Rs4795405 C>T In Iraqi Patients with Asthma

The aim of this study was to investigate the association of polymorphism of Orosomucoid-like 3 ORMDL3 rs4795405 C/T gene to the susceptibility of asthma among Iraqi asthmatic patients. Forty-five asthmatic patients (23 males and 22 females), their age 19-70 years and 35 healthy controls( 18 males and 17 females) ,their age 18-71years were selected from Wasit Province using a convenient sampling method. Genetic polymorphism of Orosomucoid-like 3 ORMDL3 rs4795405 C>T was carried out using TaqMan -PCR. both patients and control groups, the distribution frequencies of genotypes and alleles of the rs4795405 C/T gene were in Hardy-Weinberg equilibrium (P<0.05) .The most common genotype in both control and asthma patients was the heterozygous genotype CT with a percentage of 67% and 66% respectively. The genotype CC was higher in the asthmatic group (20%) compared to the control group (14%). In contrast, genotype TT, the less predominant genotype, was less in the asthmatic group were less in asthmatic group (13%) compared control group (20%).The C allele was more frequent in asthma patients than in healthy controls (53.33%vs47.14%), whereas the T allele was frequent in healthy controls than in asthma patients (52.86% vs 46.67%) with no significant differences. The association analysis displayed that the individuals carrying the homozygous CC genotype were more likely to have a increased risk of asthma with OR=1.5(CI95% 0.4537to4.9593) ,P=0.5063.The heterozygous genotypes CT was not associated with asthma with OR=1.0 (CI95%0.4103 to2.6538 ),P=0.9288 . The TT genotype decreases the association with asthma OR=0.6 (CI950.1865 to2.0302), P =0.4253. These results suggested that the T allele might play a protective role against asthma whereas the C allele might consider a risk factor in asthma. The subgroup analysis revealed that the asthma risk of females with ORMDL3 CC genotype was 2.4 fold increases the risk of asthma OR=2.4889 (CI95% 0.5478to11.3081), P= 0.2377 The TC and TT genotype decreases the association with the disease with with OR = 0.8485 (CI 95% 0.2312to3.1142), P = 0.8044 and OR= 0.2121(CI95% 0.02 to2.2473)P =0.1979 respectively. Among males, ORMDL3 CT genotype ncreased asthmatic risk among patients’ males 1.3 fold, OR= 1.3333 (CI95%0.3433 to 5.1781), P=0.6777. The genotype CC decreases the association with the disease OR=0.3810 (CI95%0.0317to 4.5813), P=0.4469. While, the homozygous TT genotype was not associated with the disease OR=1.0294 (CI95% 0,2313 to4.5814), P=0.9696. The analysis of genetic model for Orosomucoid-lik 3 ORMDL3 rs4795405 showed the recessive model (CC+CT/ TT ) increased the association with the asthma OR=1.6250 P=0.4253.The Over-dominant model(CT+TT/ CC) and the dominant model(CT+TT/ CC) decreased the association with asthma OR=0.9583,P=0.9288and OR= 0.6667 ,P=0.5063 respectively.

Relationship between polymorphism of GDF5 and CAPN1 genes in kalmyk breed cattle with economic and biological traits

The article presents the results of polymorphism of the GDF5 and CAPN1 genes in cattle of the Kalmyk breed, owned by the agricultural production company “Plodovitoe” of the Maloderbetovsky district of the Republic of Kalmykia, in the amount of 60 heads. DNA samples were isolated from whole blood taken from the jugular vein by an automatic extraction method. A real-time polymerase chain reaction was carried out to determine the polymorphism T586C of the GDF5 gene and C316G of the CAPN1 gene. In the studied herd of cattle, animals with the TT genotype predominate - 68.3 % of the population, the number of animals with the TC and CC genotypes is 21.7 % and 10 %. When studying the polymorphism of the CAPN1 gene, it was revealed that 23.3 % of the bulls of the studied population of Kalmyk cattle have the desired genotype CC, while the heterozygous genotype is present in 16.7 %, and the recessive genotype GG is present in 60 % of animals. The frequency of occurrence of the T allele of the GDF5 gene is 0.792, which exceeds the indicator of the C allele (0.208) by 58.2 %, the observed frequency of TT and CC genotypes exceeds the expected indicator by 5.6 and 5.7 %, respectively, while the indicator of the TC genotype is lower than the expected frequency by 11.2 %. The frequency of occurrence of the G allele (0.683) is 36.6 % higher than that of the C allele (0.317) of the CAPN1 gene. It is noted that the GG genotype with an index of 0.600 occurs with the highest frequency, while the CG genotype has a frequency of 0.167 (43.3 % less), the CC genotype – 0.233 (36.7 % less). The indicators of the observed frequency of the CC and GG genotypes are 13.3% higher than expected, the heterozygous genotype has an excess of the expected frequency by 26.6 %. Bulls with the TT genotype of the GDF5 gene outperformed their peers with the TC and CC genotypes in all measurements. When studying the live weight of Kalmyk cattle at the age of 15 months, a positive effect of the CC genotype of the CAPN1 gene was revealed. Thus, the group of animals with this genotype had the largest live weight and surpassed their peers with the genotypes CG (by 9.9 %) and GG (by 11.1 %).

Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients.

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (PFDR) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.

Distribution of genotypes by the growth diferential factor 9 (GDF-9) gene locus in the romanov breed sheep population

The FecG gene, also known as GDF-9 (growth factor differentiation factor 9), plays an important role in regulating reproductive function in mammals. This paper presents the results of a study of a point mutation in the differential growth factor gene in Romanov breed sheep. Mutations in exon 1 of the GDF-9 gene can lead to disturbances in ovarian development and ovulation, resulting in infertility or reduced reproductive capacity in animals. The object of the study was Romanov breed sheep in a sample of 30 individuals. For DNA extraction, venous blood samples were taken from the jugular vein. In Romanov breed sheep for the GDF-9 gene, it was found that at the G1 locus of this gene there are two alleles – G and A. Three genotypes were also identified: GG (254 bp/117 bp), AG (410bp/254/117 bp) and AA (410 bp/410 bp). The observed χ2 criterion was less than expected, therefore, the empirical and theoretical frequencies do not differ significantly, and deviations from the distribution according to the Hardy-Weinberg law are not observed. The observed heterozygosity index (Ho) was 0.27. Allele frequencies were 0,8 for G and 0,2 for A. For genotypes the following were obtained: GG – 0,66, GA – 0,27 and AA – 0,07.It can be noted that the data on the frequencies of alleles and genotypes in the population of Romanov breed sheep differ from the results for the Kulunda fine-wool, Dagestan mountain, Salsk, Lacaune and Merino breeds. The research results can be used to monitor changes in allele frequencies and genotypes in sheep during the selection process.

Genotype distribution and allele frequency of thioester-containing protein 1(Tep1) and its effect on development of Plasmodium oocyst in populations of Anopheles arabiensis in Ethiopia.

Thioester-containing protein 1 (TEP1) is a crucial component of mosquitoes' natural resistance to parasites. To effectively combat malaria, there is a need to better understand how TEP1 polymorphism affects phenotypic traits during infections. Therefore, the purpose of this study was to determine the Tep1 genotype frequency in malaria vector populations from south-western Ethiopia and investigate its effect on Plasmodium oocyst development in Anopheles arabiensis populations. Using standard dippers, Anopheles mosquito larvae were collected from aquatic habitats in Asendabo, Arjo Dedessa, and Gambella in 2019 and 2020. Collected larvae were reared to adults and identified morphologically. Female An. gambiae s.l. were allowed to feed on infected blood containing the same number of gametocytes obtained from P. falciparum and P. vivax gametocyte-positive individuals using indirect membrane feeding methods. Polymerase Chain Reaction (PCR) was used to identify An. gambiae s.l. sibling species. Three hundred thirty An. gambiae s.l. were genotyped using Restricted Fragment Length Polymorphism (RFLP) PCR and sub samples were sequenced to validate the TEP1 genotyping. Among the 330 samples genotyped, two TEP1 alleles, TEP1*S1 (82% frequency) and TEP1*R1 (18% frequency), were identified. Three equivalent genotypes, TEP1*S1/S1, TEP1*R1/R1, and TEP1*S1/R1, had mean frequencies of 65.15%, 2.12%, and 32.73%, respectively. The nucleotide diversity was ranging from 0.36554 to 0. 46751 while haplotype diversity ranged from 0.48871 to 0.63161, across all loci. All sample sites had positive Tajima's D and Fu's Fs values. There was a significant difference in the TEP1 allele frequency and genotype frequency among mosquito populations (p < 0.05), except populations of Anopheles arabiensis from Asendabo and Gambella (p > 0.05). In addition, mosquitoes with the TEP1 *RR genotype were susceptible and produced fewer Plasmodium oocysts than mosquitoes with the TEP1 *SR and TEP1 *SS genotypes. The alleles identified in populations of An. arabiensis were TEP1*R1 and TEP1*S1. There was no significant variation in TEP1*R1 allele frequency between the high and low transmission areas. Furthermore, An. arabiensis carrying the TEP1*R1 allele was susceptible to Plasmodium infection. Further studies on vector-parasite interactions, particularly on the TEP1 gene, are required for vector control techniques.

Validation of gene polymorphisms (rs2682818 and rs2043556) in has-miR-618 and has-miR-605 with the breast cancer susceptibility

BackgroundBreast cancer (BC) is one of the most frequent types of cancer and the second leading cause of cancer-affiliate death among ladies. BC is a heterogeneous sickness that is impacted by environment and genetic elements. Diagnosis in the early stages impacts treatment and patient survival rate. miRNA can play a vital role in BC's early stages of tumorigenesis. Single nucleotide polymorphism (SNP) can cause changes in miRNA expression and function, which are related to the risk of several cancers. AimThe goal of this examination is to assess the affiliation among two has-miR-605 (rs2043556A > G) and has-miR-618 (rs2682818 C > A) gene polymorphisms with the risk of BC in the Iranian ladies. MethodsOur case-control examination assessed two hundred whole blood samples of one hundred ladies with BC and one hundred healthy ladies. Hence, to assess the connection between the presence of SNP miRNA genes and the risk of BC, genotyping was done by the usage of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, then the usage of the Chi-square test of SPSS software statistically analyzed the acquired result. ResultsOur findings confirmed a statistically substantial distinction within the genotype frequency of the has-miR-618 gene polymorphism among the groups (P = 0.043), whereas no statistically substantial distinction inside the genotype frequency of the has-miR-605 gene polymorphism among the control and case (P = 0.183). In addition, the allelic frequency of two polymorphisms, (rs2043556 A > G) G allele (OR = 2.163, CI 95 % = 1.56–2.988, P = 0.022) and (rs2682818 C > A) A allele (OR = 3.997, CI 95 % = 1.584–10.081, P = 0.002) substantially enhance the risk of BC. ConclusionThe results show that the G allele of rs2043556 and the A allele of rs2682818 increase the risk of BC in the women population of East Azerbaijan province.

Drug-drug interactions between letermovir and tacrolimus in Japanese renal transplant recipients simulated using a physiologically based pharmacokinetic model.

Letermovir (LET) is a novel antiviral agent recently approved for cytomegalovirus (CMV) prophylaxis of renal transplant patients in Japan. However, its interactions with tacrolimus (TAC), an important immunosuppressant, remain ambiguous, warranting careful evaluation considering the unique genetic and physiological characteristics of Japanese patients. Therefore, in this study, we aimed to investigate the drug-drug interactions between LET and extended-release TAC (ER-TAC) in Japanese renal transplant patients via physiologically based pharmacokinetic (PBPK) modeling. We developed PBPK models for LET and TAC, including a new model for ER-TAC, using the Simcyp simulator. We also created a virtual Japanese post-transplant population by incorporating physiological parameters specific to Japanese patients, including CYP3A5 genotypes. Our model accurately predicted the pharmacokinetics of both immediate-release and ER-TAC co-administered with LET. In the Japanese population, LET significantly increased ER-TAC exposure, with the effect varying by CYP3A5 genotype. For CYP3A5*1 carrier, the area under the curve ratio ranged from 2.33 to 2.53, while for CYP3A5*3/*3 carriers, it ranged from 2.82 to 2.86. The maximum concentration ratio was approximately 1.50 across all groups. Our findings suggest reducing the ER-TAC dose by approximately 57-60% for CYP3A5*1 carrier and 65% for CYP3A5*3/*3 carriers when co-administered with LET for Japanese renal transplant patients. Moreover, the developed model incorporating population-specific factors, such as hematocrit values and CYP3A5 genotype frequencies, is a valuable tool to evaluate complex drug interactions and guide the dosing strategies for LET and TAC in Japanese patients. Overall, this study expands the application of PBPK modeling in transplant pharmacology, contributing to the development of effective immunosuppressive strategies for Japanese renal transplant patients.

Features of prooxidant/antioxidant balance disorders in patients with diabetic nephropathy — carriers of different genotypes of G894T polymorphism of eNOS gene

Objective — to determinate the state of prooxidant‑antioxidant balance in patients with type 2 diabetes mellitus with nephropathy — carriers of different genotypes of G894T (rs 1799983) polymorphism of eNOS gene. Materials and methods. 126 patients with diabetic nephropathy (DN) were examined. The control group included 20 healthy individuals. Patients with type 2 diabetes mellitus (DM) were divided into two groups depending on the eNOS rs 1799983 gene polymorphism: group I — patients with DN and G/G genotype eNOS G894T gene (n=80); group II — patients with DN and G/T and T/T genotypes eNOS G894T gene (n=46). Results. The distribution of genotypes of the rs1799983 polymorphism of the eNOS gene corresponded to the Hardy‑Weinberg equilibrium. Data analysis demonstrated a significant difference in the frequency of occurrence of genotypes and alleles of the studied polymorphism in the group of patients with DN compared with controls, which corresponds to the dominant model of inheritance (odds ratio 0.31 (95% confidence interval 0.09—0.99), p=0.045). There were significant gender differences in the frequency of genotypes and alleles of the studied polymorphism in the group of patients with type 2 DM with DN: women had a significantly lower risk of the G/T polymorphism genotype than men. The study of total antioxidant activity (TAA) revealed significantly lower values of this parameter in patients with G/G genotype of the rs1799983 polymorphism of the eNOS gene compared to carriers of the T allele (G/T+T/T genotypes). In diabetic patients with different genotypes of the rs1799983 polymorphism of the eNOS gene, the levels of total hydroperoxides (THP) did not differ significantly. Homozygous and heterozygous carriers of the T allele of the rs1799983 polymorphism of the eNOS gene had a significant increase in the prooxidant‑antioxidant balance. Conclusions. In patients with DN, the distribution of genotypes of the G894T polymorphism (rs 1799983) of the eNOS gene corresponds to the Hardy‑Weinberg equilibrium in all studied groups and does not differ significantly from European populations. In men, the risk of having a heterozygous G/T genotype of the G894T (rs 1799983) polymorphism of the eNOS gene is 3 times higher than in women (according to the dominant model of inheritance, odds ratio 0.41 (95% confidence interval 0.20—0.83), p=0.013). In carriers of G/T and T/T genotypes, a significant increase in prooxidant‑antioxidant balance was observed against the background of a decrease in total antioxidant activity, compared with carriers of G/G genotype (p&lt;0.05).

Variability of UCP1 and UCP3 uncoupling protein genes in relation to climate in indigenous populations of Siberia and the Far East

Introduction. Several studies have demonstrated a correlation between variations in genes regulating human uncoupling proteins (UCP) and environmental factors. However, information on the intra- and interpopulation diversity of allele and genotype frequencies of UCP1 and UCP3 within the territory of Russia remains insufficient. This study aims to investigate the intra- and inter-ethnic variability of genetic determinants of activity of uncoupling proteins UCP1 and UCP3, and to evaluate genotype-environment associations in the populations residing in the northeastern region of Russia. Materials and methods. Genotyping was conducted on a total of 1,698 biological specimens collected from individuals representing 22 population groups of European Russia, Siberia, and the Russian Far East. Geographical and climatic data spanning from 1940 to 2023 were gathered for each sample collection locality. Results and discussion. The spatial distribution of genetic determinants affecting the activity of UCP1 and UCP3 uncoupling proteins demonstrates a correlation with the severity of natural conditions. Three regression models of allele frequencies were constructed using climatic characteristics as predictors. All models are statistically significant (p&lt;0.05 in all cases) and explain 39%, 36%, and 64% of the variability in UCP1 (rs6536991, rs1800592) and UCP3 (rs1800849) allele frequencies, respectively. These correlations revealed by the models confirm the adaptability of UCP genes in the indigenous population groups of Northern Eurasia. Conclusion. The results of this study are consistent with the assumptions reported in scientific literature and significantly enhance existing knowledge. We observed correlations between allele and genotype frequencies of UCP1 (rs6536991, rs1800592) and UCP3 (rs1800849) genes and geographic latitude, elevation above sea level, as well as climatic indicators such as annual average rainfall, range of surface air temperatures, and the Bodman “weather severity” index. Further investigation involving a larger number of ethnic and territorial groups is necessary to better understand the factors influencing UCP gene variability formation.

A cross-sectional pilot study to estimate the frequency of minor blood group alleles and phenotypes in RhD-negative North Indian blood donors by DNA microarray analysis

Abstract: INTRODUCTION: There are scarce data on Indian blood donors with respect to blood group phenotypes using molecular diagnostic modalities. Hence, we planned to estimate frequencies of blood group alleles/phenotypes using DNA microarray analysis in the north Indian RhD-negative blood donor population. With this initial pilot study, we plan to expand it to our entire donor population. METHODOLOGY: The cross-sectional prospective study was conducted on 50 Indian blood donors (O RhD negative), to study the blood group genotype frequency. Genotyping for the most relevant red blood cell antigens (Rh, Kell, Duffy, Kidd, MNS, Lutheran, and Dombrock) was done using Bioarray Precise TypeHM Human Erythrocyte Antigen BeadChip kit containing probes directed to polymorphic sites. RESULTS: In the Rh system, the most common alleles were RHCE*e/RHCE*e (98%) and RHCE*c/RHCE*c (80%). Phenotype K-k+ (genotype- KEL*02/KEL*02) was seen in 98% of samples, Js(a-b+) (KEL*02.07/KEL*02.07) was detected in 98% (49/50) of the samples tested. Jk(a + b+) (JK*01/JK*02) was the most common phenotype (48%) in the Kidd blood group system. In MNSs system, M+N+ (GYPA*01/GYPA*02) 44% and S+s+U+ (GYPB*03/GYPB*04) 34% were the most common phenotypes detected. CONCLUSION: This pilot study shows the feasibility of genotyping a Northern Indian donor population. To the best of our knowledge, it is the first study on molecular blood grouping in Indian blood donors using the Bioarray platform.

Association of the Single Nucleotide Polymorphism 19216T/C in the TLR2 Gene (rs3804099) with Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii Infection Among Lebanese Children.

Toll-like receptors (TLRs), particularly the TLR2, take part in the elicitation of immune responses against Entamoeba histolytica. This study aimed to investigate the relationship between a specific polymorphism called rs3804099 in the TLR2 gene and E. histolytica/E. dispar/E. moshkovskii infection among Lebanese children. A case-control study encompassed 180 participants including 68 children with amebiasis and 112 matched controls. Blood samples were collected, and genomic DNA was extracted using the classical proteinase K digestion and phenol-chloroform extraction method. The variant rs3804099 was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction. The accuracy of the genotyping was supported by sequencing 5% of samples. The TLR2 rs3804099 polymorphism was identified in the studied population, and the observed genotypic distributions were consistent with Hardy-Weinberg equilibrium (P > 0.05). The frequency of the rare CC genotype was significantly higher in patients compared to the noninfected group (P < 0.01). In controls, the homozygous TT genotype was less frequent than the heterozygous CT genotype. The rare CC genotype was associated with a higher risk of amebiasis among children (odds ratios = 3.27, P = 0.002). These findings provide evidence supporting the association between the rs3804099 SNP in the TLR2 gene and E. histolytica/E. dispar/E. moshkovskii infection among Lebanese children.

Genome-wide association study of cassava brown streak disease resistance in cassava germplasm conserved in South America

Cassava (Manihot esculenta Crantz) is a vital carbohydrate source for over 800 million people globally, yet its production in East Africa is severely affected by cassava brown streak disease (CBSD). Genebanks, through ex-situ conservation, play a pivotal role in preserving crop diversity, providing crucial resources for breeding resilient and disease-resistant crops. This study genotyped 234 South American cassava accessions conserved at the CIAT genebank, previously phenotyped for CBSD resistance by an independent group, to perform a genome-wide association analysis (GWAS) to identify genetic variants associated with CBSD resistance. Our GWAS identified 35 single nucleotide polymorphism (SNP) markers distributed across various chromosomes, associated with disease severity or the presence/absence of viral infection. Markers were annotated within or near genes previously identified with functions related to pathogen recognition and immune response activation. Using the SNP candidates, we screened the world’s largest cassava collection for accessions with a higher frequency of favorable genotypes, proposing 35 accessions with potential resistance to CBSD. Our results provide insights into the genetics of CBSD resistance and highlight the importance of genetic resources to equip breeders with the raw materials needed to develop new crop varieties resistant to pests and diseases.

Polymorphism of 8-oxoguanine DNA glycosylase -1(OGG1)in Iraqi Patients with Type2 Diabetes Mellitus

Chronic hyperglycemia in type 2 diabetes mellitus leads to elevated oxidative stress. As a consequence , the accumulation of reactive oxygen species (ROS)may cause additional damage to various biological macromolecules, including DNA. Several studies have demonstrated that oxidative stress plays an important role in the pathogenesis of type2 diabetes mellitus. The aim of this study is to investigate the association of polymorphisms of 8- oxoguanine DNA glycosylase-1(OGG1) repair gene polymorphism to the susceptibility of type 2 DM in an Iraqi population with T2DM patients from Wasit Province. All samples were collected from the local community of Wasit province, Iraq. Forty five type 2 diabetes mellitus patients (22 males and 23 females) and 35 healthy controls (17 males and 18 females) were genotyped for 8-oxoguanine DNA glycosylase-1(OGG1) using PCR- RFLP technique. In both patients and control groups, the distribution frequencies of genotypes and alleles of 8-oxoguanine DNA glycosylase-1(OGG1) A/G was inconsistent with the Hardy-Weinberg equilibrium in T2DM patients(χ2=49.542,P=(0.00001); χ2=82.0185,P=(0.0001) respectively. The Cys/Cys(mt/mt) OGG1 genotype was significantly higher in patients than controls(mt/mt;33(37%)vs,0.00 in controls. The Ser/Cys (wt/mt) was 7(16%) and 6(17%) in patients and controls respectively and Ser/Ser genotypes wt/wt; decreased significantly in patients 5(11%) vs,29(83%) in controls. The wt and mt allele frequencies of OGG1were highly significant between the two groups P=0.00001. The wt allele was the major one in control group with a percent of (90.28) vs. (18.89) in patients group. Whereas the mt the frequent allele in patients with a percent of (81.11) vs. (18.89).This further analysis showed that the individuals carrying the homozygous Cys/Cys(mt/mt) genotype were more likely to have increased the risk of T2DM very significantly with OR= 190.02800 (CI95% 10.8329 to 3342.2603) ,P=0.0003. The genotypes Ser/Ser( wt/wt) and Ser/Cys(wt/mt) decrease the association with T2DM with OR=0.0259 (CI95% 0.0072 to 0.0930), and 0.8904 (CI95% 0.2701 to 2.9347 )respectively, P= 0.0001 and 0.08486 for each genotype respectively, These results suggest that mt allele may be considered as risk allele of T2DM whereas the wt allele is protective agent T2DM.Association analysis showed that the type2 diabetes mellitus risk of females with OGG1 gene Cys/Cys( mt/mt) genotype was highly significant 81.4000 fold higher than that in controls OR= 81.4000 (CI 95% 4.3089 to 1537.7322), P= 0.0033.Ser/Cys( wt/mt) genotype increase the probability of the disease with OR = 1.7647 (CI 95% 0.3745 to 8.3154), P = 0.4727.Similary,Ser/Ser(wt/wt) genotype decrease the association with T2DM with OR= 0.0091 (CI95% 0.0009 to 0.0959), P = 0.0001.Type2 diabetes mellitus patients particularly with Cys/Cys(mt/mt) genotype increases the association about more than 111 times in males patients than that in controls OR= 111.3636 ( CI95% 5.7135 to2170.6226), P = 0.0019 While, genotypes Ser/Cys(wt/mt) and Ser/Ser (wt/wt) reduce the likelihood of T2DM with OR= 0.2222 ( CI95% 0.0209 to 2.3585),P = 0.2120 and 0.0476( CI95% 0.0091 to 0.2484), P= 0.0003 respectively. the genetic model for OGG1 in comparison between T2DM patients and controls . The dominant model indicated that patients and controls of (wt/mt+mt/mt) genotype increased significantly the association with T2DM in patients: (5/7 and 33) comparing with control (29/6 and 0.00) with OR (38.666),P=0.0001.The recessive model revealed that patients carrier the genotype (wt/wt+wt/mt) declined significantly the association with the disease :(33/5 and 7) in patients versus (0.00/29 and 6) in controls,OR=0.0053,P=0.0003.The Over-dominant model showed that patients with the genotype (wt/wt+mt/mt) in creased non-significantly the association with the disease when compare patients (7/5 and 33) with controls(6/29 and 0.00) ,OR=1.123,P=0.848

Comparison of MCM6 rs4988235 Polymorphism Allele and Genotype Frequencies in Professional Football Players and a Sedentary Control Group

Comparison of MCM6 rs4988235 Polymorphism Allele and Genotype Frequencies in Professional Football Players and a Sedentary Control Group

B-236 New real-time PCR test for APOE genotyping in patients with Alzheimer’s disease before anti-amyloid therapy

Abstract Background In 2023, the US Food and Drug Administration approved LEQEMBI, a monoclonal antibody therapy targeting beta-amyloid plaques, for patients with early-stage Alzheimer’s disease (AD). However, anti-amyloid drug trials demonstrated an elevated risk for amyloid-related imaging abnormalities with cerebral edema (ARIA-E) in carriers of the AD risk allele apolipoprotein E epsilon 4 (APOE-ɛ4), especially in ɛ4/ɛ4 homozygous individuals [1-3]. Here, we report on the evaluation of a new real-time polymerase chain reaction (PCR) test for APOE genotyping. Methods The EURORealTime APOE (EUROIMMUN), which enables simultaneous testing for all six APOE genotypes (ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4) by real-time PCR, was performed using genomic DNA (gDNA) isolated from EDTA blood samples. The PCR amplification results were evaluated using the EURORealTime Analysis Software (EUROIMMUN). Samples from healthy blood donors (HBD) were used to assess intra-assay, inter-assay and between-lot precision (n=6) as well as analytical sensitivity (n=21), with each APOE genotype represented by at least one sample. Assay accuracy was analyzed by comparing genotype assignments to the results of the CE-IVD-marked EUROArray APOE (EUROIMMUN) and bidirectional Sanger sequencing using 110 samples (100 AD, 10 HBD). APOE genotype frequencies were compared between patients (100 AD) and controls (250 HBD). Results Precision testing of the EURORealTime APOE resulted in 100% correct genotype calls. Assessment of the analytical sensitivity revealed valid and correct genotype assignment in all 21 samples, confirming 1 ng/µl as the recommended minimum gDNA concentration. The analytical accuracy amounted to 100% based on agreement with the two reference methods in 110/110 cases. Comparison of the APOE genotype distribution showed a higher proportion of ɛ4 allele carriers (i.e., ɛ2/ɛ4, ɛ3/ɛ4, and ɛ4/ɛ4) in AD patients than in HBD (50.0% vs. 25.2%). The prevalence of the ɛ4/ɛ4 genotype in these cohorts was 25.0% for AD patients compared with 2.8% for HBD. Conclusions The well-established high prevalence of the APOE-ɛ4/ɛ4 genotype in AD patients, together with the increased risk of ARIA-E in these homozygous carriers, substantiates the relevance of APOE genotyping prior to anti-amyloid treatment. The EURORealTime APOE test provides sensitive and reliable determination of APOE alleles, thus presenting a suitable tool to improve risk stratification for potential LEQEMBI recipients.

Strong associations between the FGF-2 gene and productivity traits of Holstein-Friesian dairy cattle

Sustainability in dairy cattle farms depends on the efficiency of milk yield and reproductive traits. Thus, this study aimed to investigate the effect of the FGF-2/Csp6I gene and major environmental factors on these traits in Holstein-Friesian cattle. A total of 212 whole blood samples were collected from the Vena coccygea of cattle and the data obtained from these samples were used in all statistical analyses. Then, the restriction fragment length polymorphism (RFLP) method (determination of genotypes) was conducted and programs including PopGene (allele and genotype frequencies), Minitab (association analyses) and MTDFREML (variance components and genetic parameters) were used. Alleles A (0.4269) and G (0.5731) as well as genotypes AA (0.174), AG (0.505) and GG (0.321) were found, indicating that the population is polymorphic and in Hardy-Weinberg equilibrium (P > 0.05). The effect of the Csp6I polymorphism of FGF-2 gene on peak milk yield (PMY) (P < 0.01); lactation milk yield (LMY), milking time (MT), 305-day and 200-day lactation milk yield (LMY305 and LMY200), average daily milk yield (ADMY) (P < 0.05); 100-day lactation milk yield (LMY100), age of using in first breeding (AUFB) and number of inseminations per conception (NIPC) (P < 0.10) were significant. The heritability of milk yield traits and the correlation between direct and maternal heritability for reproductive traits were high. Furthermore, the breeding value of PMY was higher for the AA genotype (0.745 ± 0.292) than for the AG genotype (−0.268 ± 0.171) (P < 0.05). As a result, the A allele and AA genotype for the FGF-2/Csp6I gene had an increasing effect on milk yield without compromising reproductive performance in Holstein-Friesian dairy cattle.

Population Size in Evolutionary Biology Is More Than the Effective Size.

In population genetics idealized Wright-Fisher (WF) populations are generally considered equivalent to real populations with regard to the major evolutionary processes that influence genotype and allele frequencies. As a result we often model the response of populations by focusing on the effective size N e . The Diversity Partitioning Theorem (DPT) shows that you cannot model the behavior of a system solely on the basis of a diversity (accounting for unevenness among items) without taking richness into account. I show that the census population size (the number of adults, N c ) is equivalent to a richness, and that the effective size N e is equivalent to a true diversity. It follows logically from the DPT that we require both N e and N c to understand how drift, selection, mutation, and gene flow interact to shape the course of evolution of populations. Here I review evidence that both N c and N e affect evolutionary trajectories of populations for neutral and adaptive processes. This also influences how we should consider evolutionary potential and genetic criteria for conservation of populations. The effective size of a population is of huge importance in evolutionary biology, but it should not be the sole focus when population size is concerned. Applied evolutionary studies need to integrate N c in the equation more consistently when modeling the response to selection, mutation, migration, and drift.

Genetic Polymorphisms of COL1A1 Promoter Region (rs1800012) and TGFB1Signal Peptide (rs1800471): Role in Cervical Insufficiency Susceptibility?

A structural or functional cervix problem prevents a woman from carrying a full-term pregnancy, which leads to the disease known as cervical insufficiency. Cervical insufficiency is partially inherited, and in certain situations, variations in genes related to connective tissue metabolism may be involved. The main objective of this investigation was to describe the collagen type I alpha 1 chain (COL1A1) gene rs1800012 polymorphism and the transforming growth factor beta 1 (TGFB1) gene rs1800471 polymorphism in a cohort of patients suffering from cervical insufficiency. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays have been used to analyze the DNAs of 93 patients with cervical insufficiency and 103 healthy controls. The chi-square test was used for statistical analysis. There were significant differences in the genotype frequencies of the COL1A1 gene rs1800012 (G > T) and TGFB1 gene rs1800471 (G > C) polymorphisms between the patient and the control groups (p = 0.049 and p = 0.049, respectively). Also, the C allele of the TGFB1 rs1800471 polymorphism was significantly higher in the patient group than the control group (p = 0.016). Following clinical assessment, the COL1A1 rs1800012 polymorphism was found to be connected to the history of cerclage (p = 0.010). Additionally, the frequency of the TT/GG composite genotype of COL1A1 rs1800012/TGFB1 rs1800471 polymorphisms was significantly lower in the patient group than the control group (p = 0.049). The TT genotype of COL1A1 rs1800012 polymorphism was found to be protective against cervical insufficiency, while the C allele of TGFB1 rs1800471 polymorphism was found to predispose to the disease. It appears that the TT/GG composite genotype of COL1A1 rs1800012/TGFB1 rs1800471 polymorphisms protects against cervical insufficiency.

Human papillomaviruses in hand squamous cell carcinomas from Chilean patients

IntroductionCutaneous squamous cell carcinoma (SCC) accounts for 20% of all skin cancers and its incidence continues to increase globally. It represents 75% of non-melanoma skin cancer (NMSC) mortality. Risk factors include ultraviolet radiation (UVR) exposure, advanced age, chemical exposure, fair skin types, and immunosuppression. While most human papillomavirus (HPV) infections are associated with the development of warts, a subgroup is potentially implicated in the development of cutaneous SCC. The prevalence of alpha, beta, and gamma-HPV in Chilean patients with hand SCCs has not been previously addressed. The objective of this study was to evaluate the presence of HPV and genotyping in hand SCC from Chilean patients.Materials and methodsAn observational, cross-sectional, descriptive study was conducted. Alpha (α), beta (β) and gamma (γ)-HPV detection was performed by conventional polymerase chain reaction (PCR) in paraffin-embedded tissue samples from 52 patients diagnosed with hand SCC from Santiago, Chile. HPV genotyping was carried out via direct amplicon sequencing by Sanger method.ResultsThe most frequent carcinoma site was the dorsum of the hands (52.5%). α-HPV was not detected in these specimens, whereas β-HPV and γ-HPV were detected in 25% of the analyzed samples. The most frequent genotypes found were β-HPV 100 (38%) and γ-HPV 178 (15%). Additionally, γ-HPV 101, 162, HPV-mSK_016, HPV-mSK_083, HPV-mSK_213 and HPV-mSK249nr genotypes were detected, none of which had been previously described in cutaneous SCC.Conclusionβ-HPV and γ-HPV are detectable in 25% of hand SCCs from Chilean patients. It is important to conduct prospective studies to better elucidate the role of these viruses in the development of this disease.