Heterozygous CT Genotype Research Articles

Association between rs8192678 C/T polymorphism of the PPARGC1A gene and metabolically associated fatty liver disease in obese children living in the Moscow region

Over the past 30 years, the incidence of childhood obesity has quadrupled, leading to a rise in metabolically associated fatty liver disease (MAFLD), which has multifactorial genesis. Numerous studies highlight a significant genetic contribution to the development and severity of MAFLD. Purpose of the study. Тo determine the distribution of alleles and genotypes of the rs8192678 C/T polymorphism of the PPARGC1A gene and its relationship with the development of MAFLD in obese children living in the Moscow region. Materials and methods. The study included 87 children with exogenous constitutional obesity. The children were divided into two groups: group I - obesity without MAFLD (n = 43), group II - obesity with MAFLD (n = 44). The association of genotypes with the risk of developing MAFLD was studied in various genetic models. Results. 43 (49.4%) children had genotypes containing the T allele: 4 (4.6%) - homozygous TT genotype, 39 (44.8%) - heterozygous CT genotype. The CC genotype was detected in 44 (50.6%) children. The frequency of allele C was 73%. Carriers of the T allele have almost twice the risk of developing MAFLD than сarriers of the C allele (OR = 2.08 (95% CI: 1.05-4.24), p = 0.041). Conclusion. Тhe rs8192678 polymorphism increases the risk of developing MAFLD already in childhood, and with the homozygous TT genotype, this risk more than doubles. Studying the genetic contribution to the development of MAFLD enables a comprehensive approach to assessing individual risks of each patient.

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.

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.

CD14 gene polymorphism in COVID-19 convalescents: analysis of (C-159)T

Cluster of differentiation 14 (CD14) is a pattern recognition receptor for lipopolysaccharide of gram-negative flora and has a close relationship with toll-like receptor 4 (TLR4). The interaction between CD14 and TLR 4 leads to the synthesis of cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-á. The TLR4 receptor is associated with the penetration of the new coronavirus infection virus into the cell, additionally stimulating the expression of the angiotensin converting enzyme 2 molecule and suppressing apoptosis in infected cells. Work on the study of the (159C)T polymorphism of the CD14 gene in COVID-19 is represented by only a few publications describing observations only in the Western European region. The purpose of our study was to study the association between single nucleotide polymorphism (SNP) of the CD14 gene – (159C)T (rs2569190) and susceptibility to a new coronavirus infection in the population of the Republic of Crimea. The study included 158 patients (87 women (55%) and 71 (45%) men, average age 45.6±6.14 years) who had COVID-19. Verification of previous COVID-19 was based on anamnestic data and data from studies performed at the time of illness (PCR). The control group consisted of 85 respondents who had not suffered a new coronavirus infection. To analyze the (C-159)T polymorphism of the CD14 gene, allele-specific PCR with electrophoretic detection in a 3% agarose gel (NPF "Litekh", Russia) was used. To compare the frequencies of allele combinations, the ÷2 test and odds ratio (95% CI) were used. The distribution of CD14 mutations followed Hardy-Weinberg equilibrium (p 0.05). The results of the study showed that the distribution of CD14 gene genotypes did not differ significantly in all study groups. The dominant genotype was the heterozygous genotype CT of the (C-159)T polymorphism of the CD14 gene. The analysis showed that the presence of CT and TT SNPs was not associated with the risk of developing a new coronavirus infection (p 0.05). Conclusions. The CD14 SNP (C-159)T is not associated with a higher risk of COVID-19 infection. The distribution of occurrence of SNP variants in the group of recovered individuals did not differ significantly from that in the control group (p 0.05).

ARHGAP42 rs604723 Gene Polymorphism Is Associated With Pulse Wave Speed In Hypertension Diagnosed Subjects

Introduction: Hypertension is a systemic disease characterized by high blood pressure and an important threat for the population, as it is common and can cause serious complications. Genetic and environmental factors are involved in its development like the recently defined genetic risk factor ARHGAP42 that encodes the Rho GTPase activating protein 42. In the study, the intronic rs604723 (C/T) gene polymorphism of ARHGAP42 was investigated in relation to arterial stiffness. Methods: Peripheral blood samples, taken from 63 study group subjects with hypertension and 100 healthy subject as control, were analyzed for the presence of the ARHGAP42 rs604723 gene polymorphism by a real-time PCR method following DNA isolation. Demographic data of the study group subjects were recorded and blood pressure, ambulatory blood pressure and arterial stiffness values were measured. Results: The heterozygous polymorphic CT (~2-fold) and homozygous polymorphic TT (~1.6-fold) genotypes were found to be higher in study group subjects when compared to the control group subjects, whereby the increase of the CT genotype was statistically significant (p = 0.006). Similarly, the frequency of the polymorphic T allele was found to be higher (~1.9-fold) and statistically significant (p = 0.003) in the study group subjects. In addition, the heterozygous polymorphic CT and homozygous polymorphic TT genotypes were found to be associated with carotid-femoral pulse velocity, which is a measure of arterial stiffness (p = 0.025). Conclusion: In this study, the ARHGAP42 rs604723 (C/T) gene polymorphism was found to be associated with pulse wave speed in subjects with hypertension. It will be of interest, to investigate its association with any specific drug or drugs commonly used in anti-hypertensive therapy. Thus, it would be possible to select the appropriate drug or drugs according to the hypertensive subjects’ genotype to carry out personalized medicine in future.

Genotyping of Holstein Cows by SELL, MX1 and CXCR1 Gene Loci Associated With Mastitis Resistance.

Mastitis is a significant factor that decreases milk production in cows of different breeds in Kazakhstan. The objective of this study was to determine the genetic makeup of Holstein cows by analysing specific gene loci (SELL, MX1, CXCR1+291C>T and CXCR1+1093C>T) that are linked to resistance against mastitis. The goal was to identify cows with favourable genotypes that are less prone to udder diseases. At the SELL gene locus c.567T>C, all three genetic variants were identified in the control population with the respective frequencies: TT (0.20), CT (0.44), and CC (0.36). Genetic variation was also detected at the MX1 gene c.567T>C, CXCR1 c.+291C>T and CXCR1+1093C>T loci. Deviation from the expected Hardy-Weinberg equilibrium was observed for two gene loci, MX1 g.143182088 and CXCR1+1093C>T, with increased chi-square values of 10.6261 and 9.7137, respectively. The analysis of subclinical mastitis incidence indicates that cows carrying the heterozygous CT genotype at the L-selectin gene locus exhibit greater resistance to the disease. Animals carrying the CCCCCT genotype at the MX1 c.567T>C, CXCR1 c.+291C>T and CXCR1+1093C>T gene loci were discovered to have a significant likelihood of developing subclinical mastitis. This suggests that these genes could serve as potential indicators of susceptibility to the condition. The practical significance of this study lies in determining the frequency of genotypes linked to mammary gland morbidity in Holstein breeding farms in Kazakhstan.

A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana

BackgroundThe burden of chronic kidney disease (CKD) and kidney failure in Ghana is on the ascendency, with the prevalence of CKD estimated at 13.3%. Patients with CKD who progress to kidney failure require life sustaining kidney replacement therapy (KRT) which is almost exclusively available in Ghana as haemodialysis. Kidney transplantation is considered the best KRT option for patients with irreversible kidney failure due to its relative cost efficiency as well as its superiority in terms of survival and quality of life. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing are required.ObjectiveThis study sought to determine single nucleotide polymorphisms in CYP3A5, CYP3A4 and MDR1 genes that affect the pharmacokinetics of Tacrolimus in a population of Ghanaian patients with kidney failure.MethodThis cross-sectional study comprised of 82 kidney failure patients undergoing maintenance haemodialysis at the Renal and Dialysis unit of Korle-Bu Teaching Hospital (KBTH). Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).ResultsParticipants, 58/82 (70.73%) harbored the wildtype CYP3A5*1/*1 AA genotype, 20/82 (24.39%) carried the heterozygous CYP3A5*1/*3 AG genotype, and 4/82 (4.88%) had the homozygous mutant CYP3A5*3/*3 GG genotype. Also, 6/82 (7.32%) carried the wildtype AA genotype, 11/82 (13.41%) had the heterozygous AG genotype, and 65/82 (79.27%) harbored the homozygous mutant GG genotype of CYP3A4*1B (-290 A>G). For MDR1_Ex21 (2677 G>T), 81/82 (98.78%) carried the wildtype GG genotype, while 1/82 (1.22%) had the heterozygous GT genotype. For MDR1_Ex26 (3435 C>T), 63/82 (76.83%) had the wildtype CC genotype, while 18/82 (21.95%) carried the heterozygous CT genotype, and 1/82 (1.22%) harbored the mutant TT genotype.ConclusionSNPs in CYP3A4, CYP3A5, and MDR1 genes in a population of Ghanaian kidney failure patients were described. The varying SNPs of the featured genes suggest the need to consider the genetic status of Ghanaians kidney failure patients prior to transplantation and tacrolimus therapy.

Role of NQO1 Gene Involvement and Susceptibility of T2DM Among Saudi Arabia Population.

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia and is a significant contributor to the development and progression of diabetes. Oxidative stress has been linked to several symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, the present research aimed to evaluate the genetic abnormality of NQO1 (rs1800566, C609T) gene polymorphism, expression, and vitamin-D level assessment among Type 2 diabetes mellitus (T2DM) patients. The study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy controls. Total RNA was extracted from the whole blood using the TRIzol method, and further cDNA was synthesized, and expression was evaluated. There is a significant difference in NQO1 (rs1800566, C609T) genotype distribution among the T2DM patients and healthy controls (p = 0.04). Compared with the NQO1 CC wild-type genotype, the NQO1 CT heterozygous genotype had an odds ratio of 1.96 (1.08-3.55), and the NQO1 TT mutant type genotype had an odds ratio of 3.31 (0.61-17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p < 0.0001) and homozygous mutant TT genotype (p = 0.0004), compared with homozygous wild-type CC genotype. NQO1 mRNA expression level was also compared with vitamin D levels among the T2DM patients. T2DM patients with vitamin D deficiency had 1.83-fold NQO1 mRNA expression, while vitamin D insufficient and sufficient T2DM cases had 3.31-fold (p < 0.0001) and 3.70-fold (p < 0.0001) NQO1 mRNA expression. It was concluded that NQO1 (rs1800566, C609T) CT and TT genotypes played a significant role in the worseness of type II diabetes mellitus, and decreased expression of NQO1 mRNA expression could be an essential factor for disease worseness as well as hypermethylation could be a factor for reduced expression leading to disease severity. The decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype associated with vitamin D deficiency may contribute to disease progression.

Exploring Genetic Link of Residual Ridge Resorption in Completely Edentulous Individuals: A Prospective Case-Control Clinical Study.

Residual ridge resorption presents obstacles in prosthodontic treatment, affecting denture stability and the success of dental implants. Genetic elements, specifically the single nucleotide polymorphism (SNP) 1772C>T variant within the hypoxia-inducible factor 1 subunit alpha (HIF-1α) gene, are hypothesized to contribute to residual ridge resorption progression. Nevertheless, its impact remains insufficiently investigated, especially within the context of South Indian populations. We sought to investigate the connection between SNP 1772C>T and residual ridge resorption (RRR) among fully edentulous individuals, considering demographic factors, genotyping methodologies, and statistical evaluations. In a prospective case-control study, we recruited 100 completely edentulous participants from South India. Participants were categorized based on alveolar ridge height. Saliva samples were non-invasively collected for DNA extraction, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was employed to determine genotype distribution using the HphI restriction enzyme. The statistical evaluations comprised the utilization of chi-square and Fisher's exact tests. We observed no significant variations in genotype distributions between the case and control cohorts (CT: p=0.24; CC: p=0.65; TT: p=0.30). The heterozygous genotype CT was prevalent in both groups. Although we did not observe significant associations between SNP 1772C>T and RRR, our findings imply a genetic predisposition to residual ridge resorption that warrants further exploration. Variations in genetic susceptibility across ethnicities and the influence of other genetic variants on residual ridge resorption require additional investigation. This study lays the groundwork for personalized prosthodontic care by highlighting the potential of genetic analysis in routine dental practice to improve treatment strategies.

Association between arachidonate lipoxygenase 15,c.-292 C > T gene polymorphism and non-cystic fibrosis bronchiectasis in children: a pilot study on the effects on airway lipoxin A4 and disease phenotype

BackgroundPersistent airway inflammation is a central feature of bronchiectasis. Arachidonate 15-lipoxygenase (ALOX-15) controls production of endogenous lipid mediators, including lipoxins that regulate airway inflammation. Mutations at various positions in ALOX-15 gene can influence airway disease development. We investigated association between ALOX-15,c.-292 C > T gene polymorphism and bronchiectasis unrelated to cystic fibrosis in Egyptian children. Also, lipoxin A4 (LXA4) level in bronchoalveolar lavage (BAL) was studied in relation to polymorphism genotypes and disease phenotypes determined by clinical, pulmonary functions, and radiological severity parameters.MethodsThis was an exploratory study that included 60 participants. Thirty children with non-cystic fibrosis bronchiectasis (NCFB) were compared with 30 age and sex-matched controls. ALOX-15,c.-292 C > T polymorphism was genotyped using TaqMan-based Real-time PCR. LXA4 was measured in BAL using ELISA method.ResultsThere was no significant difference between patients and controls regarding ALOX-15,c.-292 C > T polymorphism genotypes and alleles (OR = 1.75; 95% CI (0.53–5.7), P = 0.35) (OR = 1; 95% CI (0.48-2), p = 1). BAL LXA4 level was significantly lower in patients, median (IQR) of 576.9 (147.6–1510) ng/ml compared to controls, median (IQR) of 1675 (536.8–2542) (p = 0.002). Patients with severe bronchiectasis had a significantly lower LXA4 level (p < 0.001). There were significant correlations with exacerbations frequency (r=-0.54, p = 0.002) and FEV1% predicted (r = 0.64, p = 0.001). Heterozygous CT genotype carriers showed higher LXA4 levels compared to other genotypes(p = 0.005).ConclusionsLow airway LXA4 in children with NCFB is associated with severe disease phenotype and lung function deterioration. CT genotype of ALOX-15,c.-292 C > T polymorphism might be a protective genetic factor against bronchiectasis development and/or progression due to enhanced LXA4 production.

Role of CES1 and ABCB1 Genetic Polymorphisms on Functional Response to Dabigatran in Patients with Atrial Fibrillation.

Background: Dabigatran etexilate is a pro-drug hydrolyzed into dabigatran by carboxylesterases (CES) and is a substrate of the P-Glycoprotein encoded by the adenosine-triphosphate-binding cassette sub-family B member (ABCB)1 genes. We evaluated the functional response to dabigatran according to different CES1 and ABCB1 single-nucleotide polymorphisms (SNPs) in patients with atrial fibrillation (AF). Methods: A total of 100 consecutive patients with AF taking dabigatran were enrolled by two Italian centers. A venous blood sample was drawn for genetic determinations, as well as a measurement of the diluted thrombin time (dTT) and drug plasma concentrations, at the trough and peak. The main objective was the relationship between the dTT values and CES1 rs2244613, CES1 rs8192935 and ABCB1 rs4148738 SNP while on two different dabigatran doses (110 and 150 mg BID). Results: A total of 43 patients were on a 110 mg dabigatran dose and 57 on 150 mg. The DTT values at the trough and at peak were not different among patients with different CES1 rs2244613 and CES1 rs8192935 genotypes, regardless of the dabigatran dose. In patients on 150 mg dabigatran, the dTT values at the trough were 77 (44-111) ng/mL in patients with the ABCB1 rs4148738 heterozygous CT genotype vs. 127 (85-147) ng/mL in the wild-type CC genotype vs. 110 (47-159) ng/mL in the mutant trait TT genotype (p = 0.048). In patients with the ABCB1 rs4148738 CT genotype, OR for having dTT values at a trough below the median was 3.21, 95% CI 1.04-9.88 (p = 0.042). Conclusions: ABCB1 rs4148738 CT heterozygous is associated with the reduced anticoagulant activity of dabigatran at the trough in patients receiving the higher dose regimen.

Linkage between ACE2 Gene Polymorphisms and SARS-CoV-2 infection in Burkina Faso, sub-Saharan Africa

The ACE2 gene polymorphisms (rs143936283, rs146676783, and rs4646116) in infected and noninfected persons by SARS-CoV-2 in Burkina Faso. Our cross-sectional study population comprised 137 SARS-CoV-2 infected persons and 181 non-infected persons. Three ACE2 gene polymorphisms rs143936283, rs146676783, and rs4646116, were genotyped using the real-time PCR standard TaqMan allelic discrimination technique. The association between SARS-CoV-2 infection and the polymorphisms were evaluated by a binary logistic regression. There was no association between the polymorphisms rs143936283, rs4646116 haplotypes, and SARS-CoV-2 infection in our study population. However, in the female population, the heterozygous genotype CT of rs146676783 increased by two and half the risk (OR=2.58 95%CI (1.2-5.48), p= 0.014) of being infected by SARS-CoV-2. Additionally, carrying the homozygous minor allele (genotype TT) of rs146676783 increased by more than five and half the risk (OR=5.57 95%CI (1.64-18.78), p=0.006) of being infected by SARS-CoV-2 among females. This study showed that the ACE2 gene variant rs146676783 was associated with an increased risk of being infected by SARS-CoV-2 in females, suggesting a need for further investigation to contribute to a better understanding of the African COVID-19 enigma.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Study of the effect of ACYP2 single nucleotide polymorphisms rs843711 and rs843706 in Egyptian patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a multifactorial disease with both genetic and environmental factors contributing to its pathogenesis. ACYP2 is a gene that is related to cell differentiation, apoptosis and prevention of malignant tumors. The ACYP2 gene also affects telomere length. The aim of this study was to evaluate the association between ACYP2 single nucleotide polymorphisms (SNPs) (rs843711), and (rs843706) and incidence of HCC in Egyptian HCC patients. The study included 30 patients with HCC and 30 normal controls. Detection of ACYP2 gene SNPs rs843711, and rs843706 in all study participants was done using real time polymerase chain reaction (RT-PCR). The results showed that all participants including HCC patients and controls carried the heterozygous CA (100%) of the rs843706 SNP (p&gt; 0.05). As for the rs843711, 3.3% of HCC patients had the homozygous TT genotype, 46.7% had the heterozygous CT genotype and 50% had the wild CC genotype, while in the control group, 60% had the heterozygous CT genotype and 40% had the wild CC genotype with no significant difference between both groups (p&gt;0.05). We concluded that there was no association between SNPs ACYP2 rs843706 and rs843711 and occurrence of HCC.

Genetic variations in exon 10 of ENAM and their association with early childhood caries

ObjectiveEnamelin is the largest enamel matrix protein encoded by the ENAM gene. The primary purpose of this study was to identify genetic variants in ENAM exon 10 that can alter susceptibility to early childhood caries (ECC). MethodsThis case-control study included 248 children aged 3–6 years, with 124 children diagnosed with ECC in the case group and 124 children without caries in the control group. Questionnaires were used to record demographic data, socioeconomic status, hygienic practices, and feeding practices, and a 24-h diet diary was kept. Seven polymorphisms (rs7671281, rs1738668322, rs3796703, rs3796704, rs759376039, rs775159311, and rs1738678483) in ENAM exon 10 were sequenced. ResultsThe heterozygous CT genotype of rs7671281 was significantly more common in the case group compared to the control group (odds ratio [OR], 6.1765; 95% confidence interval [CI], 2.05–18.58; P = 0.0006). Under the dominant model, the TT genotype of rs7671281 was significantly more common in the control group (OR, 6.47; 95% CI, 2.15–19.39; P < 0.001). The AG genotype of rs3796704 was significantly more common in the case group than in the control group (OR, 5.705; 95% CI, 1.60–20.25; P = 0.006). Under the dominant model, the GG genotype of rs3796704 was significantly more common in children without caries than in children with caries (OR, 6.84; 95% CI, 1.96–23.90; P < 0.001). ConclusionsThe C allele of rs7671281 and the A allele of rs3796704 can increase susceptibility to ECC.

Abstract P18: Splicing polymorphism rs12459419 modulates antibody-bound internalization of CD33 isoforms

Abstract P18: Splicing polymorphism rs12459419 modulates antibody-bound internalization of CD33 isoforms

Relationship of ACE1 and ACE2 genetic polymorphisms on SARS-CoV-2 infection and severity of symptoms in different regions of Iraq

This study was conducted in the laboratories of the Biology Department - College of Science - Tikrit University, the laboratories of the Food Science Department - College of Agriculture - University of Anbar, and the Public Health Laboratories - Anbar for the period from December 2021 AD until February 2022 AD, study involved taking samples from hospitalized COVID-19 patients of both sexes, after a confirmed positive PCR test result. As well as those lying in quarantine in three Iraqi governorates (the isolation unit in Karkh, Yarmouk and Kadhimiya hospitals, the Al-Shifa quarry hospital in Anbar, the public health laboratory in Anbar, and the quarantine hospital for thousands in Erbil), in addition to outpatient clinics. They were distributed by 30 patients and 20 healthy subjects from each governorate, with ages ranging from 18-80 years, randomly to men and women in order to determine the role of genetic polymorphisms in the ACE inhibitor gene in the study samples. The results of the genetic polymorphisms of ACE-1rs4646994, ACE-2rs2106809, and ACE-2rs4240157 showed that there were non-significant differences between the frequency of alleles and genotypes in the patient's group compared with the healthy group. The DD mutant genotype of ACE-1rs4646994 appeared in the patient's group in Baghdad and Anbar with a high percentage, while patients in Erbil showed the highest percentage of the heterozygous genotype ID compared to healthy subjects, with an OR= 0.922, OR= 2.750, and OR= 1.118, respectively, for the mutant allele D. Therefore, it is not considered a risk factor for the disease in Baghdad, in contrast to Anbar and Erbil. The polymorphism of ACE-2rs2106809, the homozygous genotype CC was dominant in patients in the aforementioned provinces and may not be considered a risk factor for the disease. The results of ACE-2rs4240157 gene polymorphism, the heterozygous CT genotype showed a high percentage in patients in Baghdad and, while in Anbar patients, the normal genotype TT appeared to be the highest percentage compared to healthy subjects. The C mutant allele in Baghdad, Anbar, and Erbil patients reached OR= 1.306, OR= 4.333, and OR= 9.00, respectively, so this allele is considered a risk factor for the disease. We can conclude from this study the role of each of the polymorphisms rs4646994 ACE-1 and rs4240157 ACE-2 in infection with COVID-19 and the severity of its symptoms according to the geographical region and race, in contrast to rs2106809 ACE-2, as it is possible to conduct clinical studies to demonstrate the role of genetic polymorphisms with Relationship to diseases depending on the region and race.

Effect of Toll-Like Receptor 9 (TLR9) in Breast Cancer Risk, Along with Hormonal Effects in Patients Receiving Radiotherapy

Introduction: Antioxidant enzyme polymorphisms and innate immune receptors have been implicated in the development of various cancer forms. This study aimed to assess the potential association between toll-like receptor 9 (TLR9) polymorphisms and female susceptibility to breast cancer. Methods: Forty female breast cancer patients from Iraq and 20 healthy volunteers were enrolled in the study. Gene polymorphisms of TLR9 rs187084 (1237T/C) were analyzed using real-time polymerase chain reaction (RT-PCR). Additionally, a hormonal study was conducted, comparing breast cancer patients exposed to radiation with a control group. The levels of follicle-stimulating hormone (FSH), estradiol (E2), and progesterone were measured. Results: The analysis revealed a non-significant increase in the prevalence of TLR9 wild TT genotypes among breast cancer patients compared to healthy individuals (72.5% vs. 90%, respectively). Conversely, heterozygous CT genotypes were significantly higher in breast cancer patients compared to healthy women (22.5% vs. 10%, P&lt;0.05). In the hormonal study, breast cancer patients exposed to radiation exhibited a significant increase in FSH levels (2.9 vs. 18.8 IU/ml), a significant decrease in E2 levels (0.232 vs. 0.910 pico/ml), and a significant increase in progesterone levels (0.910 vs. 0.732 nanogram/ml). Conclusion: The study concludes that TLR9 rs187084 (1237T/C) polymorphism variants play crucial roles in the susceptibility of Iraqi females to breast cancer. Furthermore, the observed hormonal disruptions in FSH, E2, and progesterone levels highlight potential contributors to breast cancer development, emphasizing the need for further exploration of genetic and hormonal factors in cancer susceptibility.

Study of the association of polymorphisms of the folate cycle enzyme gene with the degree of cognitive and affective disorders in patients in the post-covid period

Recently, molecular genetic studies have become widespread, and demonstrated the importance of DNA and histone methylation processes in the epigenetic regulation of gene expression. The aim of this study was to detect the association of polymorphisms of the folate cycle enzyme gene methylenetetrahydrofolate reductase (MTHGFR) with the degree of cognitive and affective disorders and the serum level of homocysteine and folic acid in 41 post-covid patients. Hematological and laboratory indices, serum concentration of C-reactive protein, D-dimer, homocysteine and folic acid were determined. MTHGFR polymorphisms for C677T and A1298C mutations were determined by polymerase chain reaction in real time. According to the MTHGFR C677T genotype variant, the examined patients were divided into 3 groups: 1) 21 persons (male/female 10/11) with homozygous CC genotype; 2) 17 ones (male/female 12/5) with heterozygous CT genotype; 3) 3 persons with a recessive homozygous TT genotype (all men). Six months after the end of the acute phase of the coronavirus disease, patients were surveyed using questionnaires to assess the psycho-emotional state: cognitive function, anxiety and depression. No significant difference was found in the average scores of cognitive function, anxiety and depression in patients of group 1 and 2. Individuals of the group 1 C677C, who had an additional recessive homozygous C1298C mutation (group 1a, n=6), were characterized by an elevated level of homocysteine, which showed a high negative correlation with serum folate (r= -0.95). A small group of individuals with the recessive homozygous T677T genotype (group 3, all men) was distinguished by an older age, the presence of cardiovascular diseases, type 2 diabetes (2 cases out of 3), more severe manifestations of COVID-19, which forces us to pay attention to potentially increased risk of complications in such patients and requires further investigation. Correlation relationships between assessments of cognitive function, anxiety, depression and serum levels of homocysteine and folate in patients with different genotypes of MTHGFR C677T were recorded. Therefore, the use of a molecular genetic approach made it possible to pay attention to the possible predisposition to hyperhomocysteinemia in individuals who have a folic acid deficiency, and different combination of alleles of the MTHGFR gene C677T and A1298C.

Interleukin-23 receptor gene polymorphisms in osteoporosis

Objectives: Osteoporosis (OP) is a usual disease with a possible genetic predisposition. IL-23 plays a role in physiological bone remodeling and regulates the activity of cells of the bone either directly or indirectly on bone-resorbing osteoclasts as well as on bone-forming osteoblasts. Recent animal and human trials have revealed the main pro-osteoclastogenic activities for the IL-23 pathway. We examined nine single nucleotide polymorphisms (SNPs) in the interleukin-23 receptor (IL-23R) in 100 OP patients and gender- and age-matched 96 healthy volunteers. The most analyzed SNPs in the recent rheumatology literature were selected. Methods: In addition to gene polymorphisms several laboratory parameters (osteocalcin, parathormone, vitamine D) were investigated. Independent Samples t-test and Mann-Whitney-U test were used to compare several demographic and clinical parameters between the groups. P-value &amp;lt; 0.05 was accepted to be statistically significant. Results: Having the heterozygous GA genotype of IL-23R rs1004819 and the heterozygous CT genotype of Il-23R rs7530511 significantly increase the risk of developing OP (adjusted OR: 3.51, p = 0.031 and OR: 2.41, p = 0.027, respectively). The wild homozygous GG genotype of Il-23R rs11209032 had higher osteocalcin levels compared with the mutant homozygous AA genotype (18.75 ± 9.76, p = 0.009). Conclusions: Our findings suggest that several IL-23R gene polymorphisms are seen more often in osteoporosis patients than in healthy volunteers. In addition, some SNPs were related to higher serum osteocalcin levels.