Heterozygous CT Genotype Research Articles

Dairy productivity of Holstein cattle with different genotypes of the osteopontin gene (<i>OPN</i>)

The study was conducted in order to study the polymorphism of the osteopontin gene (OPN) and to evaluate the indicators of milk productivity of Holstein first-calf cows with different genotypes. The work was carried out in the agricultural complex "Plemzavod im. Lenin" of the Atninsky district of the Republic of Tatarstan and the laboratory of the Department of Physiology, Biochemistry, Genetics and Animal Nutrition of the TatNIISKh FIT KAZNTS RAS. Genotyping was carried out by PCR-PDRF at the locus of the OPN-Bse1 I gene. The analysis of the genetic structure showed that the studied population is polymorphic by the OPN gene. The distribution of alleles and genotypes was as follows: C-0.432 and T0.568; CC – 14.3% (37 goals), CT - 57.8% (149 goals) and TT - 27.9% (72 goals). The highest milk yield for 305 days of lactation and a high yield of milk protein was observed in individuals with the CC genotype. During DNA testing of 258 Holstein firstcalf cows by PCR-PDRF of osteopontin gene polymorphism (OPN), it was revealed that the studied cattle population is polymorphic and is represented by all alleles and genotypes. According to the content of the mass fraction of fat and the yield of milk fat, a statistically significant superiority is observed in animals with a heterozygous CT genotype. It has been established that the C allele has a positive effect on the signs of milk productivity and the qualitative composition of milk.

Impact of XRCC3 rs861539 and XPD rs13181 gene polymorphisms on childhood acute lymphoblastic leukemia in Egyptian patients

Abstract Background There is mounting evidence that the genotypes of DNA repair proteins and susceptibility to certain malignancies are related. Few studies, however, have examined the role of the homologous repair gene X-ray repair cross-complementing group 3 (XRCC3) genotype and xeroderma pigmentosum complementation group D (XPD) in the development or prognosis of acute lymphoblastic leukaemia (ALL). Aim of the study In this study, we investigated the impact of XRCC3 rs861539 and XPD rs13181 polymorphisms on the risk of ALL. To the best of our knowledge, this is the first report of XRCC3 and XPD polymorphisms in ALL Egyptian patients. Methods Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to analyse XRCC3 rs861539 and XPD rs13181 gene polymorphisms in 96 patients with ALL and in 103 disease-free controls, who were of a similar age. Results ALL risk is lower in individuals with the homozygous variant TT genotype at XRCC3 rs861539. The heterozygous variant CT genotype of XRCC3 was connected to increased disease risk of ALL in males. Additionally, C allele frequency was noticeably higher than T allele frequency in pre B ALL. In this investigation, there was no correlation between the XPD Lys751 rs13181 polymorphism and risk of ALL. Conclusion Our research reveals that genetic variation in the genes for DNA repair may influence ALL susceptibility.

Increased susceptibility to complicated pneumonia among egyptian children with FokI (rs2228570), not TaqI (rs731236), vitamin D receptor gene polymorphism in association with vitamin D deficiency: a case-control study

BackgroundDetermining a genetic contribution to the development of complicated community-acquired pneumonia in children may help understand underlying pathogenesis. We aimed to investigate the association between two vitamin D receptor (VDR) gene polymorphisms, FokI and TaqI, and susceptibility to complicated pneumonia in Egyptian children compared to uncomplicated pneumonia. Associations with 25 hydroxy-vitamin D serum level were studied.MethodsThis was a case-control study that included 320 participants divided into 2 groups: patients and controls. The patients’ group included 100 children hospitalized with complicated pneumonia and 100 with uncomplicated pneumonia. 120 age and sex-matched apparently healthy children served as controls. The VDR FokI and TaqI polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 25 hydroxy-vitamin D level was estimated in serum using ELISA.ResultsRegarding FokI, homozygous CC genotype was more common in complicated (52%) than uncomplicated pneumonia (28%) and controls (10%) (OR = 65; 95%CI (5.13-822.63), p < 0.001) and (OR = 4.3; 95%CI (0.7-27.16), p = 0.003), respectively. Children carrying C allele possessed 3 higher odds for complicated than uncomplicated pneumonia (OR = 3.08; 95%CI (1.33–7.14), p < 0.001). Heterozygous CT genotype increased susceptibility to complicated pneumonia (OR = 13.7; 95%CI (4.6–40.1), p < 0.001), not uncomplicated pneumonia (OR = 1.56; 95%CI (0.86–2.85), p = 0.145). Among complicated pneumonia, vitamin D level was lower in CC (6.92 ± 2.6ng/ml) than CT (9.55 ± 3.2 ng/ml) and TT genotype carriers (13.13 ± 3.6ng/ml) (p < 0.001). There was no significant difference between patients and controls as regards TaqI genotypes and alleles.ConclusionIn association with vitamin D deficiency, VDR gene FokI polymorphism, not TaqI, is a genetic risk factor for complicated pneumonia in Egyptian children.

PI3K/AKT pathway-related microRNA variants in childhood acute lymphoblastic leukemia.

Dysregulation of microRNAs (miRNAs) targeting genes in the PI3K/Akt pathway has been implicated in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). However, the impact of genetic variants in these miRNAs on ALL susceptibility has not been extensively explored in the Chinese population. To address this gap, we conducted a case-control study to evaluate the association between genetic variants in five PI3K/AKT pathway-related miRNAs (miR-149, miR-126, miR-492, miR-612, and miR-423) and childhood ALL susceptibility in the Chinese population. Additionally, we investigated the effects of the rs2292832 mutation on ALL cell proliferation and apoptosis. Our analyses revealed that the miR-149 rs2292832 mutant heterozygous CT genotype was more frequent in the control group than in the ALL cases, indicating a protective effect against ALL (adjusted odds ratio [OR]=0.78, 95% confidence interval [CI]=0.63-0.97, p=.024). Stratification analyses further revealed that the miR-149 rs2292832 CC genotype was associated with an increased risk of childhood ALL in subgroups of older children, females, those with parents who never smoked or drank alcohol, those living in painted houses, those with B-ALL, and those with high-risk ALL. Finally, we observed that the rs2292832 mutation inhibited ALL cell proliferation and induced apoptosis (p=.001), providing a potential mechanism by which this genetic variant may influence ALL susceptibility. Our study highlights the significant association between the miR-149 rs2292832 genetic variant and childhood ALL susceptibility in the Chinese population. These findings expand our understanding of the complex genetic landscape underlying ALL and have implications for the development of personalized therapeutic strategies.

The Personalized Algorithm of the “Tension-Type Headache and Arterial Hypertension” Phenotype Diagnosis

The tension-type headache (TTH) and arterial hypertension (AH) are one of the most common conditions worldwide. The cumulative assessment of clinical and genetic predictors needs to be revised. The aim is designing a scale and algorithm for predicting the risk of the “TTH + AH” phenotype developing in outpatient clinics. The leading non-genetic predictors are emotional lability and personal uneasiness. The leading genetic predictor is the carriage of the minor T allele and the heterozygous CT genotype rs3782218, as well as heterozygous genotype GA rs7314935 of the NOS1 gene encoding neuronal nitric oxide synthase. There are scale and personalized algorithm for assessing the risk of the “TTH + AH” phenotype development. There is the higher the score, the higher the risk of “TTH + AH” phenotype development in hypertensive patients. The using of the presented scale and algorithm will allow timely identification of a risk group for the “TTH + AH” phenotype and avoid diagnostic errors.

Abstract 3344: Early detection biomarkers of LncRNA H19 genotypes for determining childhood leukemia susceptibility

Abstract The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. 266 childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p=0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odds ratio (OR) of 1.46 (95% confidence interval [CI], 1.08-2.14, p=0.0429) and 1.94 (95%CI, 1.15-3.31, p=0.0169), respectively (p for tread=0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p=0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Our results indicated that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia. Citation Format: Chia-Wen Tsai, Wen-Shin Chang, Chao-Chun Chen, Pei-Chen Hsu, Yun-Chi Wang, Jen-Sheng Pei, Da-Tian Bau. Early detection biomarkers of LncRNA H19 genotypes for determining childhood leukemia susceptibility [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3344.

Multiple CD59 Polymorphisms in Chinese Patients with Mycobacterium tuberculosis Infection.

A case-control study was conducted to investigate the SNPs at CD59 rs1047581, rs7046, rs2231460, rs184251026, rs41275164, rs831633, rs704700, rs41275166, and rs10768024 by sequence-specific primer-polymerase chain reaction (SSP-PCR) in 900 tuberculosis patients and 1,534 controls. The minor allele frequencies at rs2231460, rs184251026, rs41275164, and rs41275166 were extremely low both in the Cases (0.00%-0.61%) and in the Controls (0.07%-0.43%), comparatively at rs1047581, rs7046, rs831633, rs704700, and rs10768024 were notably higher both in the Cases (8.23%-48.39%) and in the Controls (8.57%-47.16%). Among the nine SNPs, only homozygous CC genotype at rs10768024 showed a significant protective effect against TB than homozygous TT genotype (OR(95% CI) = 0.59(0.38, 0.91), χ 2 = 5.779, P = 0.016), and homozygous TT and heterozygous CT genotypes showed a significant risk of TB infection in the recessive model (OR(95% CI) = 1.68(1.10, 2.56), χ 2 = 5.769, P = 0.016). Further analysis verified that rs10768024 CC genotype independently related to TB susceptibility (OR(95% CI) = 0.60(0.39, 0.91), Wald χ 2 = 5.664, P = 0.017) in multivariate logistic regression analysis, and its genetic mutation was independent of the other SNPs (r 2 = 0.00-0.20) in haplotype analysis. The first investigation of the CD59 gene and susceptibility to TB suggests a significant risk with homozygous TT and heterozygous CT genotypes at rs10768024 loci. The homozygous CC mutation at rs10768024 loci showed a significant protection against TB susceptibility.

The effects of MDR-1 gene polymorphisms on the clinical course of chronic hepatitis B infection

Aims: Chronic HBV infection is associated with high morbidity and mortality rate due to increased risk of hepatic cirrhosis and hepatocellular cancer. Treatment modilities and resistance is currently investigated. Several mechanisms were underlying in drug resistance. P-glycoprotein (P-gp), the product of multidrug resistance gene (MDR-1), is well-known mechanism of MDR phenotype. MDR gene C1236T polymorphism is associated with decreased p-gp function. The mutation of MDR gene can affect the clinical course of disease and response rate to treatment. It was aimed to investigate the relationship between MDR gene polymorphism and clinical course and treatment responses in chronic HBV infection in our study. Methods: A total of 90 (male/female:69/21) patients with chronic HBV infection under Lamivudine treatment was enrolled in this study. Mean ages were 49.8±12.6 (range:22-75) years. The patients were categorized as: Treatment responded (group 1: HBV-DNA is negative at 24th week) and treatment refractory (group 2: HBV-DNA is still positive after 24th week). Group 1 was consisted of 51 (M/F: 38/13) and group 2 was consisted of 39 (M/F: 31/9) patients. There was no significant difference between ages and genders of two groups. Histologic activity indexes (HAI), total bilirubin, AST and ALT levels, HBV-DNA titers were significantly higher in the patients in group 2 than group 1 (p&lt;0.05). Results: Genotype distributions; homozygous CC genotype was in 8 (15.7%),heterozygous CT genotype was in 37 (%72.5), homozygous TT genotype wasin 6 (11.8%) in patients at group 1. Homozygous CC genotype was in 13 (33.3%), heterozygous CT genotype was in 21 (53.8%), homozygous TT genotype was in 5 (12.8%) in patients at group 2. CC genotype was more common in group 2 than group 1 (p=0.044). C and T alleles’ frequencies in the group 1 and 2 were 51.96% and 60.26%, 48.04% and 39.74%, respectively (p&gt;0.05). The patients with YMDD mutation positive at group 2 (n:11), 5 (45%) had have CC genotype, 5 (45%) had have CT, 1 (9%) had have TT genotype.The patients with YMDD mutation negative at group 2 (n:8), 3 (37%) patients had have CC and 5 (63%) patients had have CT genotype. CC genotype was more common in the patients with YMDD mutation positive than group 1 (p=0.043). Moreover, CC genotype was more common in the patients with HBV-DNA positive at 12nd month of Lamivudine treatment than group 1 (p=0.042). Conclusion: Consequently; MDR-1 and p-gp polymorphisms are important factors in the clinical course of chronic HBV infection and may influence the treatment responses. In the current study, it was found that the CC genotype of MDR-1 gene C1236T was more common in the patients with lamivudine resistant HBV infection.

Semen quality analysis of the Airshire bulls in relation to the AH1 fertility haplotype

The results of the studies (2019-2021) of increased incidence of genetic mutations, such as fertility haplotypes, in the population that result in lower reproductive rates in dairy cattle are presented. Semen quality of the Ayrshire breed bulls was evaluated for motility and morphological indices due to rs475678587 in the UBE3B gene locus associated with the AH1 fertility haplotype. Semen samples (n = 14) were obtained from the Center of Collective Use "Genetic Semen Collection of Domestic and Foreign Cattle Breeds" of the All-Russian Research Institute of Farm Animal Genetics and Breeding (ARRIFAGB) and belonged to the animals born in 2014 and older (average age of bulls was 6-15 years). Genotyping for rs475678587 of the UBE3B gene was performed by Sanger sequencing. Animals with the heterozygous CT genotype were defined as carriers of the AH1 haplotype (AH1-C), and those with the homozygous CC genotype were defined as free of the AH1 haplotype (AH1-F). Frozen-thawed semen was evaluated according to the following parameters: total and progressive motility, percentage of normal spermatozoa. Morphological indices of sperm quality were assessed after differential staining of cellular elements of spermatozoa using a commercial kit "Diakhim-Diff Quick" (ABRIS+ scientific and production company) in sperm smears. The following indicators were taken into account: acrosomal abnormalities, abnormalities in the head, tail, and neck of the spermatozoon. Data on the indicators of native semen (motility, concentration), obtained immediately after collection, were received from the archive of the technical service of the breeding enterprise. The results of the studies have shown that according to physiological and morphological indices the semen obtained from the bulls carrying the haplotype AN1 did not differ significantly from those of the bulls free of the mutation. In terms of total motility, the semen of the haplotype fertility carrier bulls was almost 2% higher than that of the haplotype free bulls. It can be noted that the haplotype carriers of fertility bulls were generally characterized by good sperm fertility indices.

Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase with Metabolic Syndrome among Eastern Indian Women: A Case-control Study

Introduction: Polymorphisms of Methylene Tetrahydrofolate Reductase (MTHFR) gene have been associated with hyperhomocysteinaemia, which in turn may lead to hypertension, insulin resistance and abnormality of lipid metabolism. All these abnormalities are also components of Metabolic Syndrome (MetS). Thus, there is possibility of an association between MetS and MTHFR polymorphism. Literature search revealed paucity of data on this association, particularly from India. Aim: To evaluate the association of C677T polymorphism of MTHFR gene with MetS, among women of eastern Indian population. Materials and Methods: A hospital-based case-control study was conducted in the Department of Biochemistry, Calcutta National Medical College, Kolkata, West Bengal, India, between December 2016 to June 2018. Anthropometric and biochemical profiling of all 417 study subjects were done. Genetic workup was done by Polymerase Chain Reaction (PCR), using suitable primer, followed by restriction fragment length polymorphism analysis using Hinf 1 enzyme to identify MTHFR C677T polymorphism. Subjects were divided into two groups according to presence or absence of MetS as per International Diabetic Federation worldwide definition and compared with Mann-Whitney U Test. Logistic regression analysis was also performed. Results: Out of enrolled 417 female subjects, 243 were categorised as MetS group. Mean age (in years), of MetS group (48.70±9.03) was found to be significantly higher (p&lt;0.001) than that of control group (42.83±10.90). A total of 45 (25%) females with MetS exhibited the presence of heterozygous CT genotype; that was significantly higher (p=0.026) than the non MetS group 21 (14.9%). The mutant T allele frequency was also significantly higher among the subjects suffering from MetS; 45 (12.5%)compared to 21 (7.4%) in the control group (p=0.036). Multiple logistic regression analysis revealed the odds of developing MetS among subjects with heterozygous CT genotype was 7.721 times (CI: 2.38-25.05) compared to those with wild genotype. Conclusion: C677T polymorphism of MTHFR gene was associated with the occurrence of MetS among woman.

Identification of the PLAG1 polymorphisms in Peranakan Ongole cattle population

Genetic factor plays a very important role in determining of cattle performance. A gene which is reported to be controlling cattle growth and body size is pleomorphic adenoma gene 1 (PLAG1). Therefore, the goal of this study was to identify PLAG1 polymorphisms in PO cattle population. A total of 43 unproductive PO cows from the slaughterhouse at Kebumen were used in this study. Blood samples were collected individually when the cattle were slaughtered. Furthermore, DNA genome was harvested from blood samples and used as DNA template for polymerase chain reaction (PCR) targeting g.48308 C>T, g.32212 (19 bp indel) and g.45233 T>C polymorphisms. g.48308 C>T and g.45233 T>C SNPs were genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) technique and a 19 bp indel of PLAG1 was directly genotyped by observing PCR products. Both allele and genotype frequencies were calculated to test Hardy-Weinberg equilibrium (HWE) status. The results showed that g.48308 C>T SNP and 19 bp indel varied. Three genotypes of the g.48308 C>T SNP namely CC, CT and TT were found in this study and two genotypes (DD and DI) of 19 bp indel were also identified. Moreover, heterozygous CT genotype frequency of g.48308 C>T SNP was 0.51 and T allele frequency was 0.60. In term of 19 bp indel, DD genotype frequency was 0.88 and D allele frequency was 0.94. In conclusion, two polymorphisms of the PLAG1 were identified in PO cattle population.

Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position −168 of the promoter region of the protein kinase R (−168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants’ heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.

GRM8 GENE POLYMORPHISM AND STALLION SPERM QUALITY

Genome-Wide Association Studies fertility will allow further selection of animals at the genomic level, and genomic selection will allow the selection of animals with good spermatogenesis at an early age. After our GWAS, several candidate genes associated with stallion sperm quality were identified. One of these genes was the GRM8 gene. In the course of Sanger sequencing studies, four SNPs were identified in the exon of the GRM8 gene and their association with the quality of stallion sperm was carried out. For the rs1138419111 genotype, no significant differences were found in the studied parameters. According to the identified single nucleotide substitution rs1147388106, the largest volume of ejaculate was in stallions with the GG genotype. According to SNP rs395286150, stallions with the heterozygous CT genotype had the best sperm quality. Analysis of data on the SNP rs394524550 revealed a significant effect of the genotype on progressive motility. Three of the four SNPs identified in the exon of the GRM8 gene are significantly associated with such indicators of stallion sperm quality as ejaculate volume, concentration, and progressive motility. Project of the Ministry of Education and Science No. 121052600354-7.

Clinical and Genetic Features of Uncontrolled, Complicated Arterial Hypertension in Hypertensive Patients of the Aral Sea Region

The purpose of this study was to assess the clinical and genetic features of the course of hypertension, complicated by a hypertensive crisis in the inhabitants of the Aral Sea region. Methods and Results: The study included 132 patients (52 men and 80 women) with AH who applied at least 5 times (4.9±2.4) during 1 year to the Nukus Emergency Medical Care Center with a diagnosis of “Uncomplicated hypertensive crisis.” The mean age of the patients was 57.2±11.6 years, the mean duration of AH ‒ 8.85±3.4 years. The control group consisted of 50 healthy people (mean age of 52.7±6.4 years), women and men in equal proportions. A cardio Hypertension Panel of multiplex RT-PCR assay was used to detect 4 SNP [ADD1 rs4961 (G460T), GNB3 rs5443 (C825T), AGT rs4762 (C521T), and AGT rs699 (T704C)]. To assess the strength of the association between a genetic marker and AH, measured by the OR, we used multiplicative and additive models. According to the results of office BP measurement, the average SBP corresponded to AH Grade 3 (200.8±22.6 mmHg), and DBP corresponded to AH Grade 2 (105.4±7.62 mmHg). All AH patients, regardless of gender, were diagnosed with left ventricular hypertrophy and increased carotid intima-media thickness. Microalbuminuria was detected in 89 (67.4%) patients, proteinuria in 39 (29.6%) patients. Among AH patients, 88% had a high salt taste sensitivity threshold (STST) and 12% had a medium STST (χ²=269.455, P=0.0001). Analysis of the multiplicative and additive models for the AGT rs699 (Т704С) SNP showed a significant risk of AH with the carriage of the T allele (OR=3.70, 95% CI: 1.88-7.26, P=0.000) and the homozygous TT genotype and heterozygous CT genotype (OR=12.55, 95% CI: 0.72-218.80, P=0.000, and OR=2.67, 95% CI: 1.24-5.74, P=0.000, respectively). At the same time, the carriage of the C allele and CC genotype may be protective against the development of AH in individuals of the Aral Sea region. Analyzing the additive models, we also found a significant risk of AH with the carriage of the homozygous CC genotype of the AGT rs4762 (C521T) SNP (OR=5.92, 95% CI: 2.78-12.63, P=0.000). For the ADD1 rs4961 (G460Т) SNP and the GNB3 rs5443 (C825T) SNP, we did not find associations with the risk of AH. The presence of ethnic differences in the prevalence and associative links of AH candidate genes with the development of the salt-sensitivity phenotype require further extended searches in this direction, especially in the Aral Sea region.

The Link between Three Single Nucleotide Variants of the GIPR Gene and Metabolic Health.

Single nucleotide variants (SNVs) of the GIPR gene have been associated with BMI and type 2 diabetes (T2D), suggesting the role of the variation in this gene in metabolic health. To increase our understanding of this relationship, we investigated the association of three GIPR SNVs, rs11672660, rs2334255 and rs10423928, with anthropometric measurements, selected metabolic parameters, and the risk of excessive body mass and metabolic syndrome (MS) in the Polish population. Normal-weight subjects (n = 340, control group) and subjects with excessive body mass (n = 600, study group) participated in this study. For all participants, anthropometric measurements and metabolic parameters were collected, and genotyping was performed using the high-resolution melting curve analysis. We did not find a significant association between rs11672660, rs2334255 and rs10423928 variants with the risk of being overweight. Differences in metabolic and anthropometric parameters were found for investigated subgroups. An association between rs11672660 and rs10423928 with MS was identified. Heterozygous CT genotype of rs11672660 and AT genotype of rs10423928 were significantly more frequent in the group with MS (OR = 1.38, 95%CI: 1.03–1.85; p = 0.0304 and OR = 1.4, 95%CI: 1.05–1.87; p = 0.0222, respectively). Moreover, TT genotype of rs10423928 was less frequent in the MS group (OR = 0.72, 95%CI: 0.54–0.95; p = 0.0221).

Polymorphisms Detection in Heat Shock Brotein70 Gene (HSP70) and its Association with Semen Quality in Local Iraqi Goats

Heat shock protein 70 (HSP70) is a vital gene affecting semen quality traits. The study aimed to estimate the breeding values additive dominance variance of Iraqi black goat semen quality and investigate the effect of allele substitution in heat shock protein 70 gene (HSP70) carpine on some semen quality traits (volume, mass motility, a live sperm, and sperm concentration). DNA isolated from 15 Iraqi black goats was subjected to PCR amplification of the caprine HSP70 gene. Used Single-nucleotide polymorphism (SNP) to detect the variant DNA fragments that were sequenced. Synonymous Genotypes were detected on mutation locus (1528C/T). Results showed three genotypes (CC, CT, TT) frequencies of 0.53, 0.40, and 0.07, respectively, and gene frequency of 0.73 and 0.27 C and T, respectively. The population was in Hardy Weinberg equilibrium. The results showed a high level of concentration sperm for CC and CT genotype compared with TT genotype. The CC genotype was associated with negative B.V for volume ejaculate, mass motility, and live sperm percentages and was positively associated with sperm concentration. CT and TT genotypes showed positive B.V for volume ejaculate, mass motility, and live sperm but negative for sperm concentration. CC and TT genotypes showed negative dominance deviation for all traits studied, while heterozygous genotype CT showed positive dominance deviation for all semen quality traits. The highest genetic variation for live sperm (0.816) but most of this variation is from dominance variance (0.653), followed by Genetic variance for mass motility (0.481), most of it from Additive variance (0.39).

ASSOCIATION BETWEEN VASCULAR ENDOTHELIAL GROWTH FACTOR GENE POLYMORPHISMS AND THE RISK OF PREECLAMPSIA IN IRAQI PREGNANT WOMEN

Background: Vascular endothelial growth factor (VEGF) is an essential factor for angiogenesis and plays important role in placental development. Objective: To investigate the association between VEGF single nucleotide polymorphisms (SNPs) +936 Cytosine/Thymine (C/T) and -634 Guanine/Cytosine (G/C) and preeclampsia risk. Methods: A total of 50 cases of pregnant women with preeclampsia and 50 healthy pregnant women (as a control) were involved in this case control study. Blood samples were collected form each woman and the Deoxyribonucleic acid (DNA) was extracted. Amplification of VEGF gene was done by conventional polymerase chain reaction (PCR) and then detection of SNPs-634 G/C and +936 C/T were carried out by restriction fragment length polymorphism PCR (PCR-RFLP). Results: The frequency of different genotypes of VEGF SNPs +936 C/T &amp;-634 G/C are in accordance with Hardy Weinberg equilibrium. VEGF polymorphism +936 C/T appeared in 3 genotypes after digestion with restriction enzymes Cytosine Cytosine (CC), Cytosine Thymine (C/T) &amp; Thymine Thymine (TT). VEGF SNP -634 G/C appeared in 3 genotypes after digestion with restriction enzymes; those were Guanine Guanine (GG), Guanine Cytosine (GC) and CC. The heterozygous genotype CT of polymorphism +936 C/T was more frequent among preeclamptic patients than the controls (26% versus 16%). Likewise, TT genotype was more frequent among preeclamptic patients (8% versus 2%) with no significant differences. At the allelic level, the difference was more prominent. The frequency of mutant allele (T allele) was much more frequent in preeclamptic patients than controls (21% versus 10%) with a statistically significant difference (p=0.049). Although CC genotype of polymorphism -634 G/C was more frequent among preeclamptic patients than controls (14% versus 10%), the difference was not significant (p=0.704). Likewise, there were no significant differences in allele frequency. Conclusion: The study suggested that the mutant T allele of VEGF +936 C/T polymorphism was associated with increased preeclampsia risk and disease development. Keywords: Vascular endothelial growth factor, polymorphisms, preeclampsia Citation: Khaleel MF, Al-Moayad HA. Association between vascular endothelial growth factor gene polymorphisms and the risk of preeclampsia in Iraqi pregnant women. Iraqi JMS. 2022; 20(1): 106-112. doi: 10.22578/IJMS.20.1.14

The oxytocin receptor gene polymorphism rs2268491 and serum oxytocin alterations are indicative of autism spectrum disorder: A case-control paediatric study in Iraq with personalized medicine implications.

Impairment of social functioning skills is a key hallmark of autism. The neuropeptide oxytocin (OXT) is a blood-based biomarker of social functioning, and a candidate for individualized treatment of ASD. The effects of OXT on the social brain are mediated by the OXT receptor (OXTR). This study assessed the clinical utility of blood OXT serum levels and the OXT receptor (OXTR) genotype as biomarkers of autism and its severity in a pediatric population in Iraq. Blood samples were collected from patients with a clinical diagnosis of ASD (n = 60) and corresponding age and gender matched healthy controls (n = 60). All clinical samples were processed at the Department of Pathology and Forensic Medicine, Faculty of Medicine, University of Kufa in Iraq. Blood serum was assayed for OXT by sandwich ELISA. Receiver operator analysis (ROC) determined area under the curve (AUC), cutoff values, and sensitivity and specificity of OXT values for accuracy of diagnosis of ASD. Isolated genomic DNA was genotyped for the OXTR gene rs2268491(C/T) SNP using allele-specific PCR. The significance of genotype (CC, CT, and TT) and allele (C and T) distributions in different patient groups was assessed using odd ratios (OR) with 95% confidence intervals (CI) and the Chi-square test. All statistical analysis was performed used SPSS software. Study characteristics in the ASD population revealed a high level of consanguinity (36.66%), and ASD recurrence rate (11.66%) and family history (28.33%). OXT levels in patients with ASD (157.58±28.81 pg/ml) were significantly higher (p = 0.003) compared to controls (75.03±6.38 pg/ml). Within stratified ASD severity groups-OXT levels were significantly different (P = 0.032). ROC analysis determined similar AUC values for overall ASD (0.807), and stratified mild (0.793), moderate (0.889), and severe categories (0.795). The best cutoff for diagnosis of ASD was 83.8 pg/ml OXT with a sensitivity and specificity of 80% and 72.1% respectively. OXTR gene rs2268491(C/T) genotyping found that ASD patients have significantly lower (p = 0.021) genotype CC frequency and a significantly higher (p = 0.04) occurrence of the heterozygous CT genotype relative to controls. ASD subjects produced highest OXT levels with the TT genotype. T allele distribution was higher in ASD males. ASD males had significantly lower distribution of the CC genotype (48.89%) compared to females (80%) (Chi-square test: χ2 = 4.43, df = 1, p = 0.035). Whereas distribution of the CT genotype was significantly higher in autistic males (44.45%) compared to females (13.33%) (Chi-square test: χ2 = 4.68, df = 1, p = 0.03). Peripheral OXT levels and OXTR genetic alterations are potential biomarkers of social functioning in the ASD patient setting. The stratification of patients with ASD into severity categories shows significant differences both in OXT levels and OXTR (rs2268491, C/T) genotype and allele distributions, that can be sex dependent. OXT based therapies will require personalized medicine tactics to correctly identify patients with ASD who require neuropeptide boosting in social settings.

Toll- like receptor 2 polymorphism and IL-6 profile in relation to disease progression in chronic HBV infection: a case control study in Egyptian patients

Chronic hepatitis B (CHB) has a wide range of outcomes depending on host immune responses mainly Toll-like receptors (TLRs) signaling and released cytokines. Toll-like receptor 2 (TLR2) single nucleotide polymorphisms (SNPs) and interleukin 6 (IL-6) may influence the course of CHB. We aimed to elucidate the relation between TLR-2 polymorphism, IL-6 profile, and CHB progression. We analyzed TLR-2 polymorphism (SNP; rs3804099) in 185 CHB patients and 60 controls using TaqMan allelic discrimination assay. Serum IL-6 levels were assessed by ELISA. IL-6 levels were considerably higher in active CHB and cirrhotic patients compared with inactive carriers and controls (P < 0.001). IL-6 showed positive correlation with ALT and advanced fibrosis in active CHB patients (r = 0.31, P = 0.02). A significant positive correlation was noticed between IL-6 and HBV DNA PCR in all CHB groups. TT genotype of rs3804099/TLR-2 was significantly more prevalent in inactive carriers compared to active hepatitis patients (P = 0.04, OR = 0.39 and 95% CI: 0.16–0.95). Both heterozygous CT and mutant TT genotypes were significantly more frequent among inactive carriers compared to cirrhotic patients (P = 0.01, OR = 0.33, 95% CI: 0.13–0.81 and P = 0.009, OR = 0.32, 95% CI: 0.13–0.77). TT genotype was significantly related to lower IL-6 levels in active hepatitis and cirrhotic groups (P = 0.005 and P = 0.001, respectively) showing that TLR mutations would be associated with milder hepatitis activity and lower possibility for disease progression. There may be a positive association between TLR2 rs3804099 polymorphism and hepatitis B activity. IL-6 is a good indicator of CHB disease progression.

Association of Variant rs7903146(c/t) Single Nucleotide Polymorphism of Transcription Factor 7-like 2 Gene with Newly Detected Hyperglycemia in Pregnancy.

Background:Transcription factor 7-like 2 (TCF7L2) gene has a significant role in hyperglycemia in pregnancy (HIP) risk. The current study was planned with the aim to evaluate the association of single nucleotide polymorphism (SNP) rs7903146 in patients of newly detected HIP among Indian population of northern region.Methods:This study was an observational case control study done among newly detected HIP (The World Health Organization (WHO) criteria, 2013) and healthy pregnant females without diabetes. Participants from both the group were genotyped for rs7903146 (C/T) variant of TCF7L2 gene using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique.Results:A total of 71 cases of newly detected HIP were included in the study, out of which 25 (35.2%) of them were of first-time detected diabetes mellitus in pregnancy (DIP) and 46 (64.7%) were of gestational diabetes (GDM) and 100 were pregnant females without diabetes in third trimester were enrolled as controls. Average age of participants in the case group was 28.7 ± 4.0 years and the control group were 26.5 ± 3.6 years (P value 0.09). The wild homozygous CC genotype, heterozygous CT genotype and homozygous TT genotype were present in 39.4%, 53.5%, 7.1% of case group vs 53%, 43% and 4% of control group, respectively. No significant association of rs7903146(C/T) SNP of TCF7L2 gene in HIP (CC/CT, CC/TT P value 0.15, 0.38, respectively) in our population was found. There was no significant difference in the distribution of genotypes between DIP and GDM.Conclusion:This study shows no evidence of association of rs7903146(C/T) SNP of TCF7L2 gene with newly detected HIP in our population.