CC Genotype Research Articles

Study the Association between TP53 (rs12602273C>G) Gene Polymorphism with Susceptibility to the Breast Cancer in North West of Iran

Introduction: The TP53 gene on the short arm of chromosome 17p, which is known as a tumor suppressor gene, encodes the transcription factor p53, and this factor controls cell cycle progression. This study was done to assess the association of TP53 (rs12602273C>G) gene polymorphism with the risk and prognosis of breast cancer in women of northwest of Iran.
 Methods: In this case-control study, the association of TP53 (rs12602273C>G) gene polymorphism with breast cancer risk was studied in a population, including 100 patients and 100 healthy individuals was investigated by Tetra ARMS-PCR technique. The analysis of the resulting data was done using SPSS version 16 software and JavaStat online statistics package.
 Results: In the case group, the frequency of CC, CG, and GG genotypes were 81.52, 16.3, 2.17 percent, respectively and they were 79.34, 17.39, and 3.26 percent for the control group. Similarly, C and G allele frequency in case group was 89.67 and 10.32 percent and those in the control group was 88.04 and 11.95 percent, respectively. Statistical analyzes showed no association between genotypic (P>0.05) and allelic (P>0.05) polymorphism (rs12602273C>G) of TP53 gene with breast cancer. Also, the results showed that the studied polymorphism was not associated with the clinical characteristics of breast cancer patients in the Northwest of Iran (P>0.05).
 Conclusion: These research findings suggest that TP53 polymorphism of rs12602273C>G is not related to the risk of breast cancer. The association of the genotypic distribution of this SNP with the clinical characteristics of the patients was insignificant.

Production performance analysis of sheep MSTN gene C2361T locus

The myostatin (MSTN) gene exhibits significant nucleotide sequence variations in sheep, impacting growth characteristics and muscular traits of the body. However, its influence on specific growth traits in some sheep remains to be further elucidated. This study utilized single nucleotide polymorphism sequence analysis to investigate the role of the MSTN gene in meat production performance across four sheep breeds: Charolais sheep, Australian White sheep, crossbreeds of Australian White and Small-tailed Han, and crossbreeds of Charolais and Small-tailed Han. At a SNP locus of the MSTN gene, the C2361T site was identified, with three genotypes detected: CC, CT, and TT, among which CC predominated. Gene substitution effect analysis revealed that replacing C with T could elevate the phenotypic value. Comparative analysis of data from different genotypes within the same breed highlighted the superiority of CC and TT genotypes in phenotypic values, underscoring the significance of specific genotypes in influencing key traits. Contrasting the performance of different genotypes across breeds, Charolais sheep and Charolais Han hybrids demonstrated superiority across multiple indicators, offering valuable insights for breeding new sheep varieties. Analysis of gender effects on growth characteristics indicated that ewes exhibited significantly wider chest, waist, and hip widths compared to rams, while rams displayed better skeletal growth and muscle development. Additionally, the MSTN gene also exerted certain effects on lamb growth characteristics, with the CC genotype closely associated with weight. These findings not only contribute crucial insights for sheep breeding but also pave the way for future research exploring the interaction of this gene with others.

The Contribution of Double-strand Break Repair Radiation Sensitive Protein 51 Genotypes to Lung Cancer in Taiwan.

Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan. The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers. The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan.

Genetic Associations of the Polymorphic Variant of the DRD2 (rs1800497) Gene with Forms of Suicidal Behavior in Patients with Alcohol Dependence

Suicide is a serious public health problem. A deeper understanding of the underlying mechanisms and processes that lead to suicidal behavior is crucial for the development of effective preventive strategies. The study and identification of biomarkers will help in understanding the underlying processes or changes associated with suicide, however, studies linking biomarkers to suicide are limited and fragmented. Objective- To study the genetic associations of the polymorphic variant of the DRD2 gene (rs1800497) with forms of suicidal behavior in patients with alcohol dependence. Materials and methods: The association of polymorphic variants of the gene DRD2 (rs1800497) was analysed in patients with alcohol dependence syndrome, with a history of suicidal behavior and without it, living in the Republic of Bashkortostan, who were treated at the Republican Narco-logical Dispensary in the period from 2019 to 2021. Results: the presence of suicidal tendencies was detected in 39% of patients (136/344). 30% (42/136) were classified as patients with ex-ternal and internal forms of suicidal behavior, 70% (94/136) had only internal forms of suicidal behavior. Carriages of the CC and TT genotypes of the DRD2 gene (rs1800497) are characterized by a lower frequency of occurrence of all forms of suicidal behavior than carriages of СТ genotype. Also, carriages of the CC genotype of the DRD2 gene (rs1800497) are characterized by a lower frequency of occurrence of external forms of suicidal behavior than carriages of СТ and TT genotypes. Conclusions. The data we present indicate the possible contribution of genetic factors to the risk of suicidal behavior in individuals with alcohol dependence syndrome. There is a need for further research to explain the relationships between the circadian rhythm system, alcohol use disorders and suicidal behavior.

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in a North Indian Population

In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population. Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D’ and R2 values in SNP paired combinations. Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. These findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

The Influence of MTHFR C677T Variants on Neuropathy Risk Among T2dm Patients Receiving Monotherapy Metformin

Neuropathy is the most common microvascular complication among type 2 diabetes mellitus (T2DM). Metformin consumption increases neuropathy risk. The Methylenetetrahydrofolate reductase (MTHFR) enzyme has confirmed its role in neuropathy. Metformin and MTHFR could decrease folate and induce hyperhomoscysteine. One of the common variants of the MTHFR gene is C677T and its located in the exon area. This study aimed to observe the association between variant C677T in the MTHFR gene and the risk of neuropathy among newly diagnosed T2DM patients with naive metformin. This cross-sectional study recruited 103 patients. The neuropathy risk was examined according to medical judgment through Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) criteria. Genotyping C677T was performed using PCR-RFLP. This study found only one patient has a homozygote mutant, but more than 50% of patients were detected with allele mutants. There were no statistical differences in patient characteristics between CC and CT genotypes (p>0.05). Association between C677T and neuropathy risk was not significant statistically, either in the genotype model (p=0.97), allele model (p=0.82), and dominant model (p=0.91). There was still no significant association after adjusting for several confounding factors. We conclude that C677T in our population did not influence neuropathy risk. More specific criteria and laboratory parameters indicated neuropathy should be examined in the future study.
 Keywords: MTHFR, neuropathy, metformin, and T2DM

IL1B Polymorphism (rs1143634) and IL-1β Plasma Concentration as Predictors of Nutritional Disorders and Prognostic Factors in Multiple Myeloma Patients.

Multiple myeloma (MM) is a hematological neoplasm of the early precursor of B-cells. The most characteristic symptoms observed during MM include hypocalcemia, anemia, bacterial infections, and renal damage. Nutritional disorders, especially malnutrition, are noted in about 35-71% of MM patients. Interleukin 1 beta (IL-1β) is a proinflammatory cytokine responsible for muscle atrophy and lipolysis during malnutrition and cachexia. This study aimed to evaluate the usefulness of the IL1B single-nucleotide polymorphism (SNP) (rs1143634) and plasma concentration of IL-1β in the assessment of the risk of nutritional disorders and prognosis in patients with MM. In our study, 93 patients with the de novo MM were enrolled. The real-time PCR with specific TaqMan probes method was used in genotyping. The IL-1β ELISA kit was used to determine IL-1β concentration in plasma samples. Patients with the CC genotype, compared to the carriers of the other variants of the IL1B, demonstrated significantly higher concentrations of IL-1β in plasma (7.56 vs. 4.97 pg/mL), a significantly higher risk of cachexia (OR = 5.11), and a significantly higher risk of death (HR = 2.03). Moreover, high IL-1β plasma level was related to a significantly higher risk of cachexia (OR = 7.76); however, it was not significantly associated with progression-free survival (PFS) or overall survival (OS). Determination of the IL1B SNP (rs1143634) and plasma concentration of IL-1β may be useful in the assessment of the risk of cachexia and prognosis in patients with MM.

Prevalence of MTHFR Polymorphisms in Patients With Hypermobile Ehlers-Danlos Syndrome and Hypermobile Spectrum Disorders in a US Hypermobility Clinic.

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are characterized by joint hypermobility, joint subluxations and dislocations, hyperextensible skin, and chronic and progressive multiorgan comorbidities. Diagnosing hEDS and HSD is difficult because of variable phenotypes and unknown genetic etiology. In our clinic, we observed many patients with hEDS and HSD with a high serum level of unmetabolized folate, which suggests that hypermobility may be linked to methylenetetrahydrofolate reductase (MTHFR)-mediated folate metabolism. The present study aims to examine the prevalence of MTHFR polymorphisms, C677T and A1298C, among patients with hEDS and HSD. Clinical and demographic information of patients visiting our hypermobility clinic from January 2023 to July 2023 were retrospectively reviewed. Continuous variables were reported as mean ± SD and range, whereas categorical variables were reported as total count and percentage. Among 157 patients, 93% of patients were female patients, 52.2% were diagnosed with hEDS, and 47.8% were diagnosed with HSD. Interestingly, 85% of the patients had MTHFR C677T and/or A1298C polymorphisms in heterozygous or homozygous state. MTHFR 677CT/TT genotype was present in 52.9% of cases, and 49.7% of patients had 1298AC/CC genotype. In addition,14% of patients with hypermobility exhibited MTHFR 677TT genotype, 10.2% showed 1298CC genotype, and 17.2% displayed combined heterozygosity, collectively representing 41.4% hypermobile patients with two copies of MTHFR variant alleles. There is a high prevalence of MTHFR polymorphisms among patients with hypermobility, which supports the hypothesis that hypermobility may be dependent on folate status.

The association between Dental Fluorosis and COL1A2 gene polymorphism among a Tunisian Population

Dental fluorosis (DF) is a prevalent developmental defect of tooth enamel caused by exposure to excessive fluoride, with the severity dependent on various factors. This study aimed to investigate the association between DF and a specific genetic polymorphism (rs412777) in the COL1A2 gene among a Tunisian population. A case-control study was conducted from July to November 2022, involving a total of 95 participants including 51 cases and 44 controls. Dental examinations and genetic analysis were performed to assess the relationship between the COL1A2 gene polymorphism and DF.The results of allelic distribution revealed that A allele carriers were significantly protected against (DF) when compared to those with the C allele (C vs. A, p = 0.001; OR = 0.375 (0.207–0.672)). This suggests a strong correlation between the presence of the C allele and the risk of developing DF. Additionally, significant association between the CC genotype of rs412777 and an increased risk of DF was found under both codominant and dominant genetic models (P = 0.002 and P < 0.001 respectively).The findings suggest that genetic predisposition plays a relevant role in the development of DF. Further research is needed to explore the potential use of genetic markers for DF and their implications for public health. This study provides the first insights into the genetic factors associated with DF in the Tunisian population, contributing to our understanding of this prevalent dental condition.

Impact of IRGM gene promoter polymorphisms on susceptibility to chronic HBV infection.

The autophagy gene immunity-related GTPase M (IRGM) can affect the immune response against intracellular pathogens. The study was performed to determine any possible association between three IRGM single-nucleotide polymorphisms (SNPs) (rs4958842, rs4958843 and rs4958846) and chronic hepatitis B virus (HBV) infection. A total of 171 chronic HBV-infected individuals and 171 healthy controls were collected. Peripheral blood cells and Sanger sequencing were used to extract genomic DNA and determine the SNP genotypes, respectively. The C allele of rs4958843 is a risk factor for chronic HBV infection in various genetic models, including allelic, codominant and dominant models, with the following respective statistical data: allelic (T vs. C: OR=1.371, 95% CI=1.009-1.863, p=.043), codominant (TT vs. CC: OR=2.137, 95% CI=1.104-4.138, p=.024) and dominant (TT+TC vs. CC: OR=1.976, 95% CI=1.106-3.533, p=.021) models. The genotype and allele distributions of rs4958842 and rs4958846 showed no significant differences between chronic HBV infection patients and healthy controls. IRGM rs4958843 CC genotype carriers had significantly elevated values of alanine transaminase, aspartate transaminase alpha-fetoprotein and total bilirubin (OR=3.467, 95%CI=1.167-10.298), which was positively associated with the disease progression of HBV infection. Mutant allele C of IRGM rs4958843 polymorphism is associated with the risk of chronic HBV infection in the Han people in central China and contributes to the disease progression.

Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes

The adrenal androgen-metabolizing 3β-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3β-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer. To evaluate differences in mortality outcomes by HSD3B1 genetic status among men with prostate cancer. This cohort study of patients with prostate cancer who were enrolled in the Million Veteran Program within the Veterans Health Administration (VHA) system between 2011 and 2023 collected genotyping and phenotyping information. HSD3B1 genotype status was categorized as AA (homozygous adrenal-restrictive), AC (heterozygous adrenal-restrictive), or CC (homozygous adrenal-permissive). The primary outcome of this study was prostate cancer-specific mortality (PCSM), defined as the time from diagnosis to death from prostate cancer, censored at the date of last VHA follow-up. Secondary outcomes included incidence of metastases and PCSM in predefined subgroups. Of the 5287 participants (median [IQR] age, 69 [64-74] years), 402 (7.6%) had the CC genotype, 1970 (37.3%) had the AC genotype, and 2915 (55.1%) had the AA genotype. Overall, the primary cause of death for 91 patients (1.7%) was prostate cancer. Cumulative incidence of PCSM at 5 years after prostate cancer diagnosis was higher among men with the CC genotype (4.0%; 95% CI, 1.7%-6.2%) compared with the AC genotype (2.1%; 95% CI, 1.3%-2.8%) and AA genotype (1.9%; 95% CI, 1.3%-2.4%) (P = .02). In the 619 patients who developed metastatic disease at any time, the cumulative incidence of PCSM at 5 years was higher among patients with the CC genotype (36.0%; 95% CI, 16.7%-50.8%) compared with the AC genotype (17.9%; 95% CI, 10.5%-24.7%) and AA genotype (18.5%; 95% CI, 12.0%-24.6%) (P = .01). In this cohort study of US veterans undergoing treatment for prostate cancer at the VHA, the HSD3B1 CC genotype was associated with inferior outcomes. The HSD3B1 biomarker may help identify patients who may benefit from therapeutic targeting of 3β-hydroxysteroid dehydrogenase-1 and the androgen-signaling axis.

Effect of polymorphisms in the FAM151B gene on testis-related trait parameters in Hu sheep

The family with sequence similarity 151 member B (FAM151B) gene family is widely distributed in animals. This gene family encodes proteins belonging to the phosphodiesterase superfamily which plays a role in hydrolyzing intracellular second messengers, and affects the proliferation of Sertoli cells in the testis by degrading intracellular cAMP or cGMP content, thereby affecting the sperm production capacity of the testis. In this study, mutations in the FAM151B gene were screened in 491 Hu sheep to analyze the association among FAM151B gene polymorphisms testicular traits, and sperm-related parameters. A synonymous mutation (5: g.77976636 C>T), was detected in FAM151B, resulting in three genotypes, namely, CC, TT, and TC, with genotypic frequencies of 0.33, 0.05, and 0.62, respectively. This synonymous mutation was found to be significantly correlated with testicular weight, long testicular circumference, short testicular circumference, epididymal weight, and sperm count (p <0.05). In addition, individuals with CC genotypes had significant reproductive performance advantages compared with those with TC and TT genotypes. The current study shows that the FAM151B gene may play important roles in testicular development, and its SNPs are associated with testicular parameters, and sperm count, which provides important indicators for ram selection at early stage.

Impact of ABCB1 genetic polymorphism on carbamazepine dose requirement among Southern Indian persons with epilepsy.

Carbamazepine (CBZ) is one of the oldest, yet first line drugs for treating epilepsy. However, there is a large inter-individual difference in requirement of maintenance dose and one third of persons treated with antiepileptic drugs (AEDs) exhibit drug resistance to therapy. One of the proposed mechanisms for the drug resistance was increased expression of efflux transporter P-glycoprotein. The pharmacogenetic studies of drug transporters (ABCB1) done in combination therapies of AEDs were inconclusive. Hence, we have attempted to study the impact of ABCB1 3435C>T genetic polymorphism and CBZ monotherapy in persons with epilepsy (PWE) from South India, which is a genetically distinct population. With this background, this study was aimed to determine the dose of CBZ in ABCB1 3435C>T genotypes and to determine the distribution of ABCB1 3435C>T genotypes (which codes P-glycoprotein) between responders and non-responders to CBZ therapy. A cross sectional study was conducted in 200 persons with epilepsy, who were categorised as responders and non-responders according to ILAE (international league against epilepsy) criteria. Eligible participants were enrolled from the epilepsy clinic of the neurology department and five ml of blood was collected. DNA extraction and genotyping were done by phenol-chloroform method and real time polymerase chain reaction (RT-PCR), respectively. The mean maintenance dose of carbamazepine was statistically significant among different genotypes (p<0.05) of ABCB1 3435C>T (526 vs. 637 mg/day in CC vs. TT genotype). There was no significant association between ABCB1 3435C>T polymorphism (p=0.827) and CBZ resistance in PWE. Duration of disease and age of onset were found to be significant in predicting the response to CBZ therapy. We report that ABCB1 3435C>T polymorphism is significantly associated with an increase in dose requirement of CBZ in persons with epilepsy from South India.

Creatine kinase elevation in chronic hepatitis B patients with telbivudine therapy: influence of telbivudine plasma concentration and single nucleotide polymorphisms of TK2, RRM2B, and NME4.

To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine. An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600mg once daily. Plasma concentration was measured 12h after taking telbivudine using ultra-performance liquid chromatography-tandem mass spectrometry and SNPs located in RRM2B, TK2, and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant. A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07-1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers. Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase.

Cannabinoid Receptor 2 Gene Polymorphism and the Risk of Developing Rheumatoid Arthritis in Lebanese Patients.

Objective: Evidence supports a role of cannabinoid receptor 2 (CB2) in regulating the immune response. Some variations in the CB2 receptor gene (CB2) were linked to the susceptibility of developing rheumatoid arthritis (RA). The aim of this study is to assess the relationship between CNR2 rs2501431 and the risk of developing RA in Lebanese patients. Methods: A total of one hundred five Lebanese RA patients and one hundred five controls participated in the study. CNR2 was genotyped and analyzed. Results: Using χ2 test, our results show that the CC genotype was the most common (47.6%, p<0.00001) and that the C allele highly predominated (64%, p<0.00001) in the RA group compared to the control group. The relative odds ratio show that carriers of the CC genotype have more than 13-fold risk of developing RA as compared to TT. Conclusion: Our results suggest that the rs2501431 variant of CNR2 gene can be considered as a risk factor for RA development, and thus implicate the potential targeting of CB2 receptor for the treatment of RA.

Host single nucleotide polymorphisms and biomarkers of neuronal damage and inflammation in people living with HIV

ObjectivesBlood-brain barrier impairment is frequent in people living with human immunodeficiency virus (PLWHIV), affecting the penetration of target cells and antiretrovirals into the central nervous system, through transporters (e.g. ABCB1), leading to neuroinflammation. This study aimed to identify variants of genes encoding transporters able to predict neuroinflammation biomarker levels. MethodsCerebrospinal fluid (CSF) and plasma samples were obtained from PLWHIV. The CSF biomarkers were quantified by commercial assays. Genetic variants were evaluated through real-time polymerase chain reaction (PCR). ResultsA total of 107 PLWHIV (163 samples) were included in the study: 79% were male, median age was 48.5 years, CD4% was 25%, and HIV-associated neurocognitive disorder (HAND) was observed in 17.8%. The ABCB1 2677G>T genetic variant showed a different allelic distribution according to the clinical group (P = 0.026). In linear regression analyses, HIV-related central nervous system disorders, ABCG2 1194+928CC genotype, log viral load, CSF-to-serum albumin ratio, β-1,42 levels, and CSF proteins were retained in the final model as factors independently associated with CSF neopterin levels; CSF proteins and integrase inhibitor use were associated with CSF tau level in the multivariate model. Phospho-tau regression analysis reported the ABCB1 2677GT/TT genotype and CSF proteins as predictors in the final model; sex, protease inhibitors, neopterin, and ABCB1 2677 GT/ TT genotype were predictors in the multivariate regression for β-1,42. ConclusionsFor the first time, pharmacogenetic and clinical features were found to be predictors of neuro-inflammation biomarkers.

The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia.

Polymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL). This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated. A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity. Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.

Protective Role of TRPC3 Gene Polymorphism (rs10518289) in Obstructive Sleep Apnea Hypopnea Syndrome Among Hypertensive Patients.

BACKGROUND Obstructive sleep apnea-hypopnea syndrome (OSAHS) presents a significant health concern, particularly among individuals with essential hypertension (EH). Understanding the genetic underpinnings of this association is crucial for effective management and intervention. We investigated the relationship between TRPC3 gene polymorphisms and susceptibility to OSAHS in patients with EH. MATERIAL AND METHODS We enrolled 373 patients with EH hospitalized at the First Affiliated Hospital of Xinjiang Medical University between April 2015 and November 2017. Patients were categorized into EH (n=74) and EH+OSAHS (n=299) groups according to the apnea-hypopnea index. Sequenom detection technology was used for TRPC3 gene single-nucleotide polymorphism genotyping, including genotypes at rs953691, rs10518289, rs2292232, rs4995894, rs951974, and rs4292355. RESULTS Sex, smoking history, alcohol history, hypertension duration, fasting blood glucose, urea, creatinine, total cholesterol, HDL-C, LDL-C, glycosylated hemoglobin, 24-h mean systolic BP, and 24-h mean diastolic BP were not significantly different between the 2 groups (P>0.05); however, age, BMI, triglyceride levels differed significantly (P<0.05). No significant difference was detected in distribution frequency of polymorphisms of TRPC3 gene between the 2 groups (P>0.05), while genotype, dominant genotype, and recessive genotype at rs10518289 and alleles at rs4292355 differed significantly (P<0.05). Logistic regression analysis showed age, BMI, and CG+GG genotypes at rs10518289 were risk factors for OSAHS in patients with EH. Interaction between TRPC3 (rs10518289) and obesity was not a risk of OSAHS with EH (P>0.05). CONCLUSIONS CC genotype of rs10518289 in the TRPC3 gene could be a protective genetic marker of OSAHS, and CG+GG genotype may be a risk genetic marker of OSAHS with EH.

Variants in 3p24.3 predicts the risk of early neurological deterioration in large artery atherosclerotic stroke

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP–SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49–0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.

Interleukin-6 Gene (-174 G&gt;C) Polymorphisms in Patients with Chronic Hepatitis C Virus; A Case-Control Study

Background: Recent studies have suggested that polymorphisms in the Interleukin (IL)-6 gene promoter might be linked to chronic hepatitis C virus (HCV) infection, potentially affecting the infection's outcome. Objectives: The purpose of this study was to determine whether the genetic variant of IL-6 gene polymorphisms (-174 G&gt;C) is associated with HCV in patients compared to control subjects. Methods: Seventy-one patients infected with HCV and 79 healthy individuals referred to a hepatitis clinic in Mashhad, northeast Iran, were enrolled in the study. Blood samples were collected, and laboratory tests, including enzyme-linked immunosorbent assay (ELISA) for HCV antibodies and reverse transcription polymerase chain reaction (RT-PCR) for confirming HCV-positive results, were conducted. Genomic DNA was extracted from whole blood, and the ARMS-PCR method was used for genotyping the IL-6 gene polymorphisms (-174 G&gt;C). Statistical analyses were performed using SPSS version 21 software. Results: The C allele was found to be more frequent in HCV-infected patients compared to controls (P &lt; 0.05; odds ratio [OR] = 2.91, 95% CI: 1.85 - 3.16), but this association was not significant after adjusting for confounders. Additionally, in a recessive model analysis (CC vs. GG + GC), the CC genotype was more prevalent among HCV-infected patients than in healthy individuals, though not significantly (P = 0.21; OR = 2.91, 95% CI: 0.55 - 15.53). The GG polymorphism was the most common genotype in both groups (P = 0.44), while the CC genotype was the least common (P = 0.12). Conclusions: The IL-6 gene polymorphism at this position may impart a certain level of risk for HCV infection, with carriers of the C allele potentially more susceptible to this infection. However, to further elucidate the role of this polymorphism in HCV, a larger cohort of HCV-infected patients and healthy individuals may be required.