Polymorphism In Promoter Region Research Articles

Biochemical investigation of FOXP3 genetic polymorphism and its association with biochemical parameters in pre-eclampsia patients.

This study addresses the pivotal question of the association between FOXP3 gene polymorphism and pre-eclampsia (PE), employing the Tetra ARMS PCR method for analysis. PE, a multifaceted disorder marked by hypertension and organ dysfunction during pregnancy, led to an exploration of FOXP3 due to its integral role in immune regulation and its implication in various autoimmune and inflammatory disorders. The primary objective was to discern the relationship between FOXP3 gene polymorphism (rs2232365) and the risk of PE. Recruiting 200 PE patients and 100 healthy pregnant women as controls, genomic DNA was extracted from peripheral blood samples, and FOXP3 promoter region polymorphism was meticulously examined using the Tetra ARMS PCR method. The results revealed significant differences in FOXP3 gene polymorphism between PE patients and healthy controls. Specifically, certain alleles and genotypes were more frequent in PE patients, suggesting a potential genetic predisposition to this disorder. Our findings showed that rs2232365 A/G variant was found to be associated with PE under the overdominance model [OR=1.89, CI 95%= 0.99-3.60, P<0.05]. The heterozygous genotype (A/G) of FOXP3 (rs2232365) was associated with increasing the level of clinical and biochemical markers in mild and severe PE patients when compared to controls. Thus, the FOXP3 (rs2232365) A/G variant can be considered a substantial risk factor for PE.

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.

Gene Polymorphism Of TNF-A (Rs1799964) In Aborted Women With Respiratory Disease In Al-Diwaniyah Province

Background: TNF-α, a proinflammatory cytokine, plays a significant role in the etiology of various illnesses. The encoding gene is found on chromosome 6's short arm in the major histocompatibility complex class III region. Polymorphisms in the TNF-α gene promoter region are believed to impact illness susceptibility and severity. This review summarizes the research on the association between TNF-α gene and receptor polymorphisms and respiratory illness development. This study aim to determine of gene polymorphism of TNF-α in aborted women with respiratory diseases. Methods : The study was carried out for 100 pregnant women, including 60 aborted women with and without respiratory diseases, and 40 women as healthy control group. Genotypes in TNF-α T&gt;C SNPs were identified using self- designed nested T-ARMS PCR tests. Sequencing validated randomly chosen PCR results that represented unique genotypes in TNF-α SNPs. Results : The results of TNF-α (rs1799964) C/T SNP genotyping between aborted women with respiratory diseases and healthy control revealed that the heterozygous C/T genotype was a significant risk factor with an OR of 6.28, while the homozygous TT genotype was non-significant (OR= 2.09). Conclusion : The rs1799964 TNF-α polymorphisms are possible genetic risk factors of respiratory diseases and might be its predictive markers.

Olanzapine-induced Metabolic Syndrome and its Association with -759C&gt;T Polymorphism of the HTR2C Gene in Iraqi Schizophrenic Patients

The hazardous metabolic effects of treating schizophrenia patients with olanzapine comprise serotonin 2C receptor (5-HT2C) antagonists. Metabolic side effects of antipsychotic drugs, including lipid abnormalities, disturbed glucose metabolism, and weight gain, can have a major impact on treating psychiatric patients. The intent of this study was to investigate whether there is an associated link between the genetic polymorphism at -759C&gt;T in the promoter region of the 5-hydroxytryptamine 2C receptor (HTR2C) gene and the metabolic syndrome driven by olanzapine in schizophrenia patients. A cross-sectional study that involved fifty hospitalized patients with schizophrenia. The patients were split into two groups (metabolic and non-metabolic) according to the classification criteria of the metabolic syndrome. The HTR2C promoter region polymorphism was identified through sequencing using the Sanger method after polymerase chain reaction amplification of the extracted deoxyribonucleic acid. Even though none of the genotypes of the -759C&gt;T variant are associated with the propensity to develop metabolic syndrome, there is a significant difference in the -759C&gt;T variant's T allele (p-value = 0.001). The presence of the T allele in the -759 C/T variant was significantly associated with developing metabolic syndrome. Keywords: Schizophrenic patients, Olanzapine, Genetic polymorphism, 5-hydroxytryptamine 2C receptor (HTR2C) gene, -759C&gt;T.

Pharmacogenomics of 3,4-Methylenedioxymethamphetamine (MDMA): A Narrative Review of the Literature.

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative with notable psychoactive properties and emerging therapeutic potential, particularly for treating post-traumatic stress disorders (PTSD) and substance use disorders. However, its use remains controversial due to inter-individual variability influenced by both environmental and genetic factors. In this context, pharmacogenomics could play a crucial role in guiding MDMA treatment by identifying individuals with genetic predispositions affecting their response to MDMA. Tailoring treatment plans based on individual's genetic makeup may enhance therapeutic outcomes and minimize adverse effects, leading to safer and more effective use of MDMA in clinical settings. Literature analysis reveals that the influence of genetic variants within genes encoded for enzymes involved in MDMA metabolism and/or pharmacodynamics (PD) targets have been relatively under-investigated in humans. Some studies have pointed out associations between MDMA-induced effects and polymorphisms. For example, the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and cardiovascular MDMA-induced effects. Similarly, polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with several MDMA-induced adverse effects including mood disorders. However, despite these findings, only a few associations have been highlighted. Furthermore, some genes encoded for MDMA targets have been only poorly investigated, representing a significant research gap. These observations underscore the need for large-scale, controlled pharmacogenomics studies focusing on a broad panel of genes involved into MDMA pharmacokinetics and PD. Such studies could provide critical insights for optimizing MDMA's therapeutic use and minimizing its risks.

MTHFR as a Novel Candidate Marker for Litter Size in Rabbits.

Litter size is a significant economic trait during animal reproduction. This current study attempted to decipher whether MTHFR promotes the apoptosis of granulosa cells (GCs) and inhibits their proliferation by investigating the effects of the MTHFR gene using flow cytometry and a Cell Counting Kit-8 (CCK-8) assay. MTHFR is linked with ovarian follicle development in the reproductive performance of 104 female New Zealand rabbits. We observed that MTHFR could regulate the mRNA of follicular development-related genes (TIMP1, CITED1, FSHR, GHR, HSD17B1, and STAR) with a qRT-PCR, and we observed the protein expression of CITED1 and GHR using a western blot (WB) analysis. The dual luciferase activity assays helped identify the core promoter region of the MTHFR gene, and the polymorphism of the MTHFR promoter region was studied using Sanger sequencing. The results indicated four single nucleotide polymorphisms (SNPs) within the core promoter region, among which the g.-680C>A locus was significantly associated with both the total and alive litter sizes. Additionally, the CC genotype was associated with the largest total and alive litter sizes, compared to the CA and AA genotypes (p < 0.05). In conclusion, this study investigated the effects of MTHFR on ovarian granulosa cells and its association with selected reproductive parameters in rabbits. The results provide a theoretical foundation for the use of MTHFR as a molecular marker in rabbits.

Single nucleotide polymorphisms in the KRT82 promoter region modulate irregular thickening and patchiness in the dorsal skin of New Zealand rabbits

BackgroundWhile rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype.ResultsThe results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy − Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the − 600 to − 1200 segment, in which the four SNPs were located.ConclusionsThe morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.

Genetic Polymorphism of Interleukin-6 in Asymptomatic and ICU-Admitted COVID-19 Patients in Sulaymaniyah Province, Kurdistan Region of Iraq.

Background: The global pandemic of Coronavirus Disease 2019 (COVID-19) has resulted in significant fatality rates. Clinical outcomes for affected individuals range from being asymptomatic to severe illnesses requiring intensive care unit (ICU) admission. Among the various factors contributing to the variation in clinical outcomes, host genetics play a prominent role. Interleukin-6 (IL6), a key player in immune responses, has been identified as having a crucial impact on viral infections, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, certain variations known as single nucleotide polymorphisms (SNPs) in the IL6 promoter region have been found to significantly influence IL6 expression and the severity of viral infections. Materials and Methods: To explore the relationship between these genetic variations and COVID-19 in asymptomatic and ICU-admitted Kurdish patients, genetic sequencing was performed to determine the genotypes of nine IL6 SNPs. Results: The study findings revealed that although the proportion of the GG genotype of rs1800795 was slightly higher in asymptomatic COVID-19 cases, the difference was not statistically significant (chi2 = 2.666, p = 0.236). Notably, Kurdish patients displayed a uniform genetic makeup (monomorphic) for the dominant alleles of rs2069830 (C), rs142759801 (C), rs2069857 (C), rs2069829 (G), rs2234683 (G), rs13447446 (T), rs527770772 (C), and rs13447445 (C). Furthermore, patients carrying the haplotype GCGGCTCCC were found to have a 0.481-fold higher likelihood of being asymptomatic with COVID-19 (p = 0.016, OR = 0.481). Conclusions: This study demonstrates that the rs1800795 SNP is not statistically associated with COVID-19 at the genotype level. However, the presence of the dominant G allele of rs1800795 in the haplotype was found to be statistically associated with asymptomatic COVID-19 patients.

4D label-free quantitative proteomic analysis identifies CRABP1 as a novel candidate gene for litter size in rabbits†.

In commercial rabbit breeding, litter size is a crucial reproductive trait. This trait directly determines the reproductive ability of female rabbits and is crucial for evaluating the production efficiency. We here compared differentially expressed proteins of in the ovary tissue from New Zealand female rabbits with high (H) and low (L) litter sizes by using 4D label-free quantitative proteomic technology and identified 92 differential proteins. The biological functions of these proteins were revealed through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Most distributions of GO and KEGG were related to reproduction, growth development, and metabolism. Furthermore, a novel candidate gene cellular retinoic acid binding protein-1 (CRABP1), which was highly expressed in the L group, was selected for further biological function verification. The Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis revealed that CRABP1 can promote granulosa cell (GC) apoptosis and inhibit GC proliferation. Furthermore, qRT-PCR and western blotting analysis revealed that CRABP1 regulates the genes (HSD17B1, Wnt-10b, FSHR, TAF4B, BMP15, and BMP6) and protein (Wnt-10b) associated with steroid hormone synthesis and follicle development. The PCR product direct sequencing method revealed single nucleotide polymorphisms in the core promoter region of CRABP1. Luciferase activity assays revealed that the transcriptional activity of the GG genotype was significantly higher than that of the TT or TG genotype. Different genotypes are accompanied by changes in transcription factors, which indicates that T-359G polymorphism can regulate CRABP1 expression. In general, we identified litter size-related genes and revealed the mechanism underlying the effect of CRABP1 on litter size. CRABP1 serves as a key factor in the reproductive capacity of rabbits and can act as a molecular biomarker for the breeding of New Zealand rabbits.

Identification of the domestication gene GmCYP82C4 underlying the major quantitative trait locus for the seed weight in soybean.

A major quantitative trait locus (QTL) for the hundred-seed weight (HSW) was identified and confirmed in the two distinct soybean populations, and the target gene GmCYP82C4 underlying this locus was identified that significantly associated with soybean seed weight, and it was selected during the soybean domestication and improvement process. Soybean is a major oil crop for human beings and the seed weight is a crucial goal of soybean breeding. However, only a limited number of target genes underlying the quantitative trait loci (QTLs) controlling seed weight in soybean are known so far. In the present study, six loci associated with hundred-seed weight (HSW) were detected in the first population of 573 soybean breeding lines by genome-wide association study (GWAS), and 64 gene models were predicted in these candidate QTL regions. The QTL qHSW_1 exhibits continuous association signals on chromosome four and was also validated by region association study (RAS) in the second soybean population (409 accessions) with wild, landrace, and cultivar soybean accessions. There were seven genes in qHSW_1 candidate region by linkage disequilibrium (LD) block analysis, and only Glyma.04G035500 (GmCYP82C4) showed specifically higher expression in flowers, pods, and seeds, indicating its crucial role in the soybean seed development. Significant differences in HSW trait were detected when the association panels are genotyped by single-nucleotide polymorphisms (SNPs) in putative GmCYP82C4 promoter region. Eight haplotypes were generated by six SNPs in GmCYP82C4 in the second soybean population, and two superior haplotypes (Hap2 and Hap4) of GmCYP82C4 were detected with average HSW of 18.27g and 18.38g, respectively. The genetic diversity of GmCYP82C4 was analyzed in the second soybean population, and GmCYP82C4 was most likely selected during the soybean domestication and improvement process, leading to the highest proportion of Hap2 of GmCYP82C4 both in landrace and cultivar subpopulations. The QTLs and GmCYP82C4 identified in this study provide novel genetic resources for soybean seed weight trait, and the GmCYP82C4 could be used for soybean molecular breeding to develop desirable seed weight in the future.

Association of polymorphisms of IGF1 promoter with growth and fertility performance in PB1 parent line of broiler chicken variety

Blood samples from 180 birds pertaining to a single generation of PB1 parent line were collected for present study. The birds were raised under standard management and different growth variables were recorded up to 20 weeks of age. Age at first egg and egg production till 40 weeks of age was recorded in females. PCR-RFLP analysis was used to screen individuals with polymorphisms in IGF1 promoter region and three genotypes AA, AC and CC were identified at frequencies of 0.79, 0.18 and 0.03, respectively. CC homozygotes were lower with respect to their performance in growth and fertility traits. Sequencing results of both alleles revealed T244G transversion mutation in the C allele. Gene regulation analysis confirmed that such transversion resulted in non-binding of Oct-1 transcription factor at 241 to 250 bp in C allele, causing down regulation of the gene. The mutations in the promoter sequence affected the transcriptional gene regulation affecting growth and fertility performance.

Association of 5-HTTLPR With Post-Traumatic Stress Disorder in US Service Members

Objective Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members. Methods Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44. Results Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, P = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers (P < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups (P > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal (P < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score (P < .001). Conclusion Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.

Behavior Physiology of Workplace Bullying and It’s Role to Job Satisfaction and Psychologycal Distress among Workers at Water Supply Company

Individuals strive to fulfill their essential needs by working. Every company has different work environment. The work environment tends to have impact on each individual. One of the key issues that usually occur at workplace is bullying. Workplace bullying can happen to anyone while both bullies and their victims may experience psychological effects from bullying. This study aims to see the effect of workplace bullying on job satisfaction and psychological distress among water supply company employees. This research design is quantitative using cross sectional design. The results showed that the psychological distress variable played a significant role in workplace bullying (p. &lt;0.05). However, the job satisfaction variable does not contribute to workplace bullying (p. &gt; 0.05). The serotonin trasporter-linked promoter region (5-HTTLPR) polymorphism of the SLC6A4 gene consists of an insertion/deletion that creates a short (S) 14 repeat or a long (L) 16 repeat allele. Genotype profile on one’s serotonergic system is correlated by their dominance in the community. Individuals with allele LL type is more likely become bullies when they are encouraged by the environment. In contrast, individuals with SS allele type with in a characteristic of low transcription activity at transporter serotonin gene tend to become bullying victims in their workplace due to they more vulnerable to stress. Employee with amygdala which easily triggered and intimidated by the dominant individuals, more likely to experience workplace bullying. Those employee who work in supportive workplace show higher job satisfaction and they are not distress psychologically.

CCR5 promoter region polymorphisms in systemic lupus erythematosus.

This study investigated the impacts of CCR5 promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing CCR5 genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European-derived and 93 African-derived) and 375 controls (243 European-derived and 132 African-derived) were genotyped for the CCR2-64I G>A (rs1799864), CCR5-59353 C>T (rs1799988), CCR5-59356 C>T (rs41469351), CCR5-59402 A>G (rs1800023) and CCR5-59653 C>T (rs1800024) polymorphisms through polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the CCR5 haplotypes and as a possible confounding factor in the binary logistic regression. European-derived patients showed a higher frequency of CCR5 wild-type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [p=.003 (OR 3.5, 95%CI 1.6-7.5) and 2.0% vs. 7.2% (residual p=2.9E-5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African-derived patients and controls [10% vs. 20.5% (residual p=.003), 29.4% vs. 17.4% (residual p=.003) and 3.9% vs. 0.8% (residual p=.023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African-derived group and when all patients were grouped for comparison [pcorrected =.012 (OR 3.0; 95%CI 3.0-333.3) and pcorrected =.0006 (OR 6.8; 95%CI 1.9-24.8), respectively]. In conclusion, this study indicates that CCR5 promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European-derived patients and as a susceptibility factor for class IV nephritis in African-derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African-derived patients, which could modify the CCR5 protein expression in specific cell subsets.

Interleukin 10 (IL10) promoter region polymorphism is associated with IL10 serum concentrations and processing speed in healthy community-dwelling older adults

Inflammation is repressed by interleukin 10 (IL10), a potent anti-inflammatory cytokine, and unchecked inflammation can have detrimental effects on cognition. In healthy older adults enrolled in the Australian Research Council Longevity Intervention (ARCLI) cohort we explored whether a known functional single nucleotide polymorphism (SNP) in the promoter region of IL10, −1082 G/A (rs1800896), was associated with reaction times on computerized cognitive testing that included elements of processing speed (i.e., reaction time). Participants were aged 60–75 years (240 females, 158 males), free of dementia and psychiatric disorders, and provide a blood sample. Processing speed was measured using the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB), which includes measures of reaction time (in milliseconds, ms) on six tasks. Blood-derived DNA was genotyped for the IL10 rs1800896 SNP and presence of the APOE E4 allele. General linear models for each SUCCAB subtest were fitted, with age, sex, education (years), APOE E4 carrier status, and IL10 genotype as independent variables. Carriers of the IL10 AA genotype had significantly slower reaction times on multiple tests compared to carriers of the minor allele (AG, GG) and lower IL10 serum levels. Although IL10 SNPs have not been detected in Alzheimer’s disease genome-wide associated studies, these results support further exploration of IL10 mechanisms as a possible resilience factor.

TPO Gene Expression in Relation with Promoter SNPs in Iraqi Patients with Hyperthyroidism

Background: Thyroid peroxidase (TPO) gene mutations are one of the most common causes of thyroid disorders. Objective: To investigate the effect of genetic polymorphisms in the TPO promoter region on gene expression in early-diagnosed hyperthyroid patients. Methods: Genomic DNA was extracted from 100 blood samples (75 hyperthyroid patients and 25 healthy controls), then the TPO promoter region was amplified and sequenced for genotyping rs2071399, rs2071400, and rs2071403 SNPs. Total RNA was also isolated, and cDNA synthesis was performed to determine quantitatively the expression of TPO by using qPCR. The level of TPO antibodies in serum was determined by using an enzyme-linked immunosorbent assay (ELISA). Results: The prevalence of hyperthyroidism in women was significantly higher than in men, as were serum levels of TPO-Abs. There was a significant increase in serum TPO-Abs in hyperthyroid patients (235.29 IU/ml) compared with healthy controls. Genotypes of three SNPs (rs2071399 G/A, rs2071400 C/T, and rs2071403 A/G) in the TPO promoter region were TPO rs2071399 AG and GG, and rs2071400 CT and TT genotypes were more frequent in hyperthyroid patients. There are no significant differences between rs2071403 polymorphic and non-polymorphic genotypes among hyperthyroid patients and healthy controls. The rs2071399 G/A and rs2071400 C/T gene promoter polymorphism significantly down-regulated constitutive TPO gene expression in hyperthyroid patients, but rs2071403 A/G has no major effect on gene expression. Conclusion: There was an association between the mutation in the promoter region of TPO and the incidence of hyperthyroidism.

Psychobiological screening among patients affected by prostate cancer: Identification of potential psychobiological markers.

Prostate cancer is a common oncological disease of old age with the highest rates of incidence among males older than 65 years old. Diagnosis and treatment may be associated with the onset of adjustment, depressive, and anxiety disorders. The comorbidity with depression and anxiety may lead to a higher risk of suicide, and mortality as well as lower adherence to medical treatments and adverse functional outcomes in patients affected by urologic cancers. The role of genetic vulnerability and pre-morbid personality in predicting the development of mental disorders during cancer disease is debated. For instance, some genetic polymorphisms of the serotonin transporter-related promoter region (5-HTTLPR polymorphism) are associated with higher vulnerability for mental disorders as well as personality traits of neuroticism; both factors are potentially useful for identifying risk of depressive and anxious symptoms among cancer patients. This communication proposes the development of individualized psychobiological approaches to identify possible 'psychobiological' markers associated with the risk of mental disorders in prostate cancer patients.

Evaluation the -174G>C Genetic Polymorphism of Interleukin-6 in Iranian Patients with Chronic Lymphocytic Leukemia.

Interleukin-6 (IL-6) is involved in inflammation and has a significant role in chronic lymphocytic leukemia (CLL) progression. Accordingly, IL-6 level may increase in CLL-affected patients compared to healthy individuals. The -174G>C single nucleotide polymorphism (SNP) in IL-6 promoter region has been related to differences in IL-6 transcription. Therefore, we investigated the possible association of IL-6 polymorphism with CLL. We examined the -174G>C SNP in IL-6 gene and studied its possible relationship with CLL in affected patients and in healthy controls using Amplification Refractory Mutation System- polymerase chain reaction genotyping method. IL-6 plasma level was measured in both studied groups. According to the results, IL-6 mean plasma concentration was increased significantly in the CLL patients compared to the controls. However, 174G>C genotype of the IL-6 gene was not associated with CLL. Furthermore, there were no significant differences in the distribution of allele and genotype frequencies between the CLL-affected patients and the controls (P>0.05). Our study showed that -174G>C SNP in promotor of IL-6 gene could not be considered a risk factor for CLL. Larger prospective studies should be performed to confirm our results.

Genetic Polymorphism in TNF-α Promoter Region: Its Association with Severity and Susceptibility to Rheumatoid Arthritis in Iraqi Patients with Active Disease

Objectives: To study the prevalence of rs1799964 (-1031 T/C) and rs361525 (- 238 G/A) SNPs and their effect on the disease activity, severity, and cytokines production in newly diagnosed Iraqi rheumatoid arthritis patients.&#x0D; Patients and Methods: sixty-three patients were diagnosed by a specialist physician while attending the rheumatology unit and twenty control participated. The inflammatory markers were measured and PCR amplification and sequencing were performed to demonstrate TNF-α SNPs.&#x0D; Results: Regarding (-1031 C/T) SNP, the TT genotype and allele C were significantly present in the controls, and the CT genotype was distributed significantly in the patients. The TT genotype was mostly distributed in the mild-moderate group, while the CT genotype and allele C were significantly distributed in the severe group. DAS28, TNF-α, IL-1, and ACPA were significantly associated with this SNP. While non-significant differences appeared in the analysis of -238 G/A SNP.&#x0D; Conclusion: The presence of the CT genotype and C allele of) -1031 C/T( was associated with susceptibility to RA. While the CT genotype and C allele were associated with more severe disease. Also, TT genotype was associated with less severe disease. Furthermore, an association between -1031 C/T and the inflammatory markers and DAS28 was reported.

Role of tumor necrosis factor-alpha -238 G>A promoter region polymorphism on recurrent miscarriage: An association study and meta-analysis.

Recurrent miscarriage (RM) is defined as the loss of two or more consecutive pregnancies. A functional SNP, -238G>A in the promoter region of TNF-α, affects the gene transcription activity with implications on human pregnancy. Previous limited studies, linking the TNF-α -238 G>A to the risk of recurrent miscarriage have been inconclusive. The PCR-RLFP technique was used to evaluate this polymorphism in 199 RM cases and 215 control women from Amritsar, Punjab. For a meta-analysis, a total of 13 eligible studies (including the present study) comprising 2947 cases and 2933 controls were included. To evaluate the association among different genetic models, odds ratio with a 95% confidence interval (CI) and chi-square were used. Genotype and allelic frequency did not differ significantly between both groups (p=.07 and p=.24, respectively). In the present meta-analysis, a significant association was found with the recessive model (OR-1.78 CI:1.24-2.55, p=.002). Although, TNF-α -238 G>A polymorphism did not provide any risk in the case-control study but provided risk towards the development of RM with the recessive genetic model in the pooled analysis.