Differences In Allele Distribution Research Articles

UCP2 45-bp insertion/deletion polymorphism and obesity phenotype in the Lebanese population: a preliminary study

BackgroundObesity is a significant health concern in Lebanon, contributing to various chronic diseases. Uncoupling Protein 2 (UCP2) plays a critical role in regulating metabolism, and genetic polymorphisms in the UCP2 gene, such as the 45-bp insertion (I)/deletion (D) polymorphism, may influence susceptibility to obesity. This study aims to assess the association between the UCP2 45-bp I/D polymorphism and obesity in a sample of the North Lebanese population. DNA was extracted from peripheral blood of 123 subjects that were categorized into "non-obese" and "obese" groups, with further stratified analysis based on age and physical activity levels. UCP2 45-bp I/D variants were screened using polymerase chain reaction (PCR). ResultsThe genotype frequencies of the UCP2 45-bp I/D polymorphism were as follows: D/D (46.3%), I/D (46.3%), and I/I (7.4%), with a minor allele frequency of 0.30. Statistical analyses, including Chi-squared tests and logistic regression, were conducted to explore the association between the UCP2 polymorphism and obesity. After adjusting for body mass index confounders and stratifying by physical activity and age, no significant differences were found in genotypic distributions: Stratum 1 (S1: irregular exercise, age < 40, P = 0.157), Stratum 2 (S2: irregular exercise, age ≥ 40, P = 0.192), and Stratum 3 (S3: regular exercise, age < 40, P = 0.160). Additionally, there were no significant differences in allelic distributions across these strata (S1: P = 0.514; S2: P = 0.869; S3: P = 0.681). Gender was also not associated with the UCP2 45-bp I/D polymorphism.ConclusionsThis study found no significant association between the UCP2 45-bp I/D polymorphism and obesity in the North Lebanese population, suggesting that this genetic variation may not play a major role in obesity risk. These results underscore the need for larger, region-wide studies to better assess the genetic contribution of UCP2 to obesity in Lebanon.

The prognostic difference study on the individualized clopidogrel administration in Hmong and Dong patients based on the CYP2C19 gene polymorphism after percutaneous coronary intervention.

This study explored the distribution characteristics of CYP2C19 gene polymorphism among Hmong and Dong patients in the Qiandongnan region of Guizhou province after percutaneous coronary intervention (PCI). The aim was to assess the clinical impact of individualized clopidogrel administration based on CYP2C19 genotypes. A total of 208 patients were classified into ultra-fast, fast, intermediate, and slow metabolic groups. They were randomly assigned to clopidogrel individualized administration (IA) or conventional treatment (CA) groups. Patients were followed for 6 months to evaluate major adverse cardiovascular events (MACE) and adverse reactions. The CYP2C19 genotype distribution was in Hardy-Weinberg equilibrium, showing consistency in the population. While no significant ethnic differences were found in genotype and metabolic distribution, allele distribution varied, with Hmong patients exhibiting a higher proportion of CYP2C19*1 alleles than Dong patients. Following individualized administration, the IA group demonstrated lower incidences of non-fatal myocardial infarction and emergency revascularization compared to the CA group. Bleeding events were higher in the IA group, but the total MACE incidence was lower. No statistical difference in MACE and adverse drug reactions (ADR) was observed in the CA group across metabolic types, but MACE incidence was higher in intermediate and slow metabolic groups. In the IA group, no significant difference in MACE was noted among metabolic types, but ADR incidence varied significantly, particularly in dyspnea. The study highlighted significant CYP2C19 allele distribution differences between Hmong and Dong patients post-PCI in Qiandongnan. Patients with slow metabolic profiles demonstrated higher MACE incidence with conventional clopidogrel dosage, whereas CYP2C19-guided therapy reduced MACE without increasing bleeding risk. These findings supported clinical individualized clopidogrel administration in post-PCI patients in the Qiandongnan region, contributing to rational clopidogrel use.

АССОЦИАТИВНАЯ РОЛЬ ПОЛИМОРФИЗМА RS121908987 ГЕНА PRKAG2 В РАЗВИТИИ СИНДРОМА WPW

The study of cardiac arrhythmias and conduction is one of the most urgent and important tasks, since these diseases are often the cause of sudden cardiac death. We assumed that the study of the contribution of "predictor genes" of heart rhythm and conduction disorders would expand knowledge about the etiology and pathogenesis of these diseases. Thus, the purpose of our research was to study the contribution of the rs121908987 polymorphism of the PRKAG2 gene to the development of WPW syndrome. Material and methods: 200 patients with VPU syndrome were examined, among them men n=97 [18:32.66;81]; women n=103 [18;47,92;83]. All patients underwent clinical, laboratory, somatometric, instrumental studies, as well as molecular genetic studies DNA isolation was performed by the standard phenol-chloroform method. Genotyping of the PRKAG2 gene was performed by PCR-PDRF analysis (polymerase chain reaction-polymorphism of restriction fragment lengths). Statistical data processing was carried out using the Excel application software package, Statistica for Windows 10.0, IBM SPSS 20.Differences in the frequency distribution of alleles and genotypes of the PRKAG2 gene between the groups were assessed using the χ2 criterion. The relative risk of disease for a specific allele or genotype was calculated as the odds ratio (OR). Results: a statistically significant predominance of the heterozygous GA genotype in patients with VPU syndrome, compared with those in the control group (8 and 2%, respectively; Table 1). There was also a statistically significant predominance of allele A carriers in the group of patients with VPU syndrome by 4%, compared with those in the control group (2%). The risk of developing PRKAG2 genotype GA syndrome, estimated by OSH, was 2.09 times higher (95% CI 1.88–2.32; p &lt;0.001 compared with genotypes GG and AA, and in carriers of the A allele – 2.04 times higher (95% CI 1.90–2.19; p &lt;0.001) compared with allele A (see Table 2). Conclusions: The results of the study confirmed the contribution of polymorphism rs121908987 of the PRKAG2 gene to the development of VPU syndrome.

Association of combined -344T/C and K173R polymorphisms in aldosterone synthase gene with type 2 diabetes mellitus in the Moroccan population.

Background: Aldosterone synthase (CYP11B2) is crucial for aldosterone production, and variations in its gene may influence type 2 diabetes mellitus (T2DM) development. This study explores the link between two single nucleotide polymorphisms (SNPs) in the CYP11B2 gene - -344T/C and K173R and T2DM in the Moroccan population . Methods: The research involved 86 individuals with T2DM and 75 control subjects. Genotyping for the -344T/C and K173R SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis . Result: Results indicated significant differences in the genotype and allelic distribution of the CYP11B2 K173R polymorphism between T2DM patients and control subjects, with P-values of 0.02 and 0.04, respectively. The -344T/C polymorphism showed no significant genomic level differences, but its allelic variations were statistically significant (P=0.01), indicating a notable association between the C allele and T2DM. Furthermore, the K173R polymorphism was found to significantly increase T2DM risk, with a 2.34-fold higher risk in individuals carrying the KR genotype. The study also examined the combined effect of these SNPs. The dominant model analysis (TT vs. TC+CC and KK vs. KR+RR) showed significant differences between T2DM patients and controls for both SNPs. Additionally, a haplotype-based analysis revealed that the C-R haplotype was associated with an increased risk of T2DM. Conclusion: Our study suggests a significant association between the CYP11B2-K173R polymorphism and T2DM in the Moroccan population. Conversely, while the CYP11B2 -344T/C polymorphism exhibits a significant difference in allelic distribution, no significant difference is observed at the genomic level.

Evaluation of relationship between TMPRSS2 p.(Val197Met) variant and COVID-19 susceptibility and severity

BackgroundThe World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a global pandemic on March 11, 2020. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has killed millions of people and had a terrible effect on society. The transmembrane protease serine 2 (TMPRSS2) enzyme is essential in the initial phases of the interplay between the SARSCoV-2 and the host cells by assisting viral entrance.MethodsThis observational case–control study involved 150 participants, 100 adult patients with COVID-19, 50 of whom appeared healthy and had no history of or symptoms of COVID-19 infection when the study was conducted. Between January and April 2022, patients were taken as inpatients in isolation units or through recruitment from the COVID-19 clinic at Kasr Al-Ainy Cairo University Hospitals. According to the National Institutes of Health guidelines (2021), they were categorised into three categories: mild, moderate, and severe. TMPRSS2 p.(Val197Met) variant genotyping was evaluated using TaqMan Real-Time PCR.ResultsThe study showed a substantial difference between the mild and severe COVID-19 patient groups regarding their TMPRSS2 (p.Val197Met) genotypes (P value = 0.046). The C allele was significantly more prevalent in the mild, moderate and severe COVID-19 patient categories (77.8%, 89.7% and 91.7%, respectively) and the control group (80%). Meanwhile, the T allele was more prevalent in the mild (22.2%) and control (20%) groups. There was a statistically significant difference in allelic distribution between the mild and severe groups (P value = 0.034).ConclusionThe study showed a connection between the TMPRSS2 gene variant p.(Val197Met) and the degree of illness. We concluded that the T(mutant) allele was protective against severe COVID-19 because it was linked to lesser disease severity.

The effect of genetic variation and mRNA expression of interleukin-17A gene on susceptibility to asthma.

Analyzing the genetic variation and mRNA expression of interleukin-17A (IL-17A) gene and its impact on asthma susceptibility was the purpose of this study. 120 asthma patients were selected as the asthma group, and another 120 healthy individuals who underwent physical examination were selected as the health group; Compare the cytokine levels and mRNA expression of IL-17A between two groups, as well as the clinical indicator total immunoglobulin E (TIgE) levels; The genotype and allele distribution frequency of IL-17A Single-nucleotide polymorphism locus rs2275913 and rs8193036 were compared between the two groups; Compare the serum IL-17A and TIgE levels of different genotypes at rs2275913 and rs8193036 loci; and logistic regression was used to evaluate the impact of IL-17A on asthma susceptibility. The serum levels of IL-17A, TIgE, and IL-17AmRNA expression in the asthma group were higher than those in the healthy group (P<0.05). There were three genotypes of AA, AG and GG at rs2275913 locus, and the frequency distribution between the two groups was significant (P<0.05), and the frequency of A Allele frequency in asthma group was higher than that in healthy group (P<0.05). There are three genotypes of CC, CT, and TT at the rs8193036 locus, and there was no significant difference in the frequency distribution between the two groups (P>0.05). There is no difference in the frequency distribution of alleles C and T between the two groups (P>0.05). The levels of IL-17A and TIgE in the rs2275913AA genotype were higher than those in the AG and GG genotypes (P<0.05); There was no difference in IL-17A and TIgE levels among different genotypes of rs8193036 (P>0.05). The rs2275913 polymorphism was associated with asthma susceptibility and is an independent risk parameter for asthma susceptibility. Upregulation of serum IL-17A and TIgE, as well as overexpression of IL-17A mRNA, were closely related to asthma susceptibility in asthma patients. The rs2275913 polymorphism had a significant role in increasing the risk of asthma, and variant allele A may be a susceptibility factor for increasing asthma risk.

Associations between GRM7 polymorphisms and obesity in patients selected for sleeve gastrectomy.

Obesity is a worldwide problem in which genetic factors have a prominent role. We have selected two single nucleotide polymorphisms (SNPs) within glutamate metabotropic receptor 7 (GRM7) gene, namely rs6782011 and rs779867 to weigh their association with obesity in an Iranian cohort. The distribution of rs6782011 alleles was significantly different in the obese patients from normal controls (P < 0.0001; 434 obese patients vs. 297 normal controls). Distribution of alleles was also measured between sex-based groups of obese patients and controls. We detected remarkable differences between female obese cases and female control subjects (P < 0.0001; 374 female obese cases vs. 216 female normal controls); nevertheless, the difference in allele distribution was not significant for male cases compared with corresponding normal controls (p = 0.47; 60 male patients vs. 81 normal males). Contrariwise, distribution of rs779867 alleles was not significantly different between total obese patients compared with normal controls (P = 0.21; 434 obese patients vs. 297 normal BMI controls). There was also no significant difference for female and male obese patients compared with female and male normal BMI controls. Thus, GRM7 can be considered as a risk locus for obesity.

The importance of SOCS1 - 1478 CA/del polymorphism and expression in breast cancer: a case-control study in the north of Iran.

This project aimed to evaluate the relationship between the suppressor of cytokine signaling-1 (SOCS1) - 1478 CA > del genetic variation and breast cancer susceptibility. Moreover, we investigated the SOCS1 mRNA expression level in cancerous tissues. A total of 100 patients with breast cancer and 120 healthy individuals were selected. Genomic DNA was extracted from blood. SOCS1 genotyping and relative gene expression were performed using ARMS-PCR (Amplification-Refractory Mutation System-Polymerase Chain Reaction) and real-time PCR, respectively. In breast cancer patients, the prevalence of genotype frequencies of SOCS1 (- 1478 CA > del) CA/CA, CA/del, and del/del was 52, 31, and 17%, respectively. Among controls, the distribution of CA/CA, CA/del, and del/del was 63, 15, and 22%, respectively. The chi-square test reported that a significant difference was observed in the genotypic distribution of SOCS1 (- 1478 CA > del) polymorphism between cases and controls (χ2 = 8.08, P = 0.01). In addition, the presence of the CA/del genotype was associated with an elevated risk of breast cancer (in the codominant model: OR 2.51; 95% CI 1.27-4.96, P = 0.007 and in the over dominant model: OR 2.54; 95% CI 1.32-4.90, P = 0.005). However, there was no significant difference in allelic distributions between the groups (P > 0.05). There was no significant difference in the breast cancer risk associated with the dominant and recessive genetic models when the reference was CA/CA and CA/CA + CA/del genotype, respectively (P = 0.09 and P = 0.38). Moreover, the expression of SOCS1 decreased in cancerous tissues as compared to the adjacent non-cancerous tissues (P < 0.0001). In conclusion, a functional SOCS1 promoter polymorphism (- 1478 CA > del) may affect breast cancer susceptibility.

Association between angiotensin I converting enzyme gene polymorphisms and risk of autism in Iranian population

BackgroundAutism spectrum disorder (ASD) encompasses a group of neurodevelopmental disorders that are described by substantial complications in social, interactive, and behavioral functions. MethodsIn the current study, we have used a candidate gene approach for appraisal of association between polymorphisms within angiotensin I converting enzyme (ACE) gene and risk of ASD. Tetra-primer amplification-refractory mutation system (ARMS)-PCR method was used for identification of rs4359 genotypes. The rs1799752 (I/D) genotypes were defined using two rounds of PCR and electrophoresis. ResultsThe differences in allele distribution of both rs4359 and rs1799752 in the ASD patients versus controls was significant (P = 0.016 and P = 0.0004 by Pearson chi-square test from 2 × 2 contingency tables for allele distribution of rs4359 (T vs. C) and rs1799752 (D vs. I), respectively). The differences in allele distribution was also calculated at gender level between ASD patients and controls by chi-square test. There was no significant difference between female patients and female controls for rs4359 alleles (P = 0.07); moreover, the comparison of allele distribution for rs4359 was not significant for male patients compared with male controls (P = 0.145). The rs4359 was associated with risk of ASD in co-dominant model (TT vs. CC: OR (95% CI) = 1.239 (1.051–1.46), P value = 0.01; TC vs. CC: OR (95% CI) = 1.337 (1.076–1.661), P value = 0.0009). This SNP was associated with ASD in dominant model as well (TT + TC vs. CC: OR (95% CI) = 1.571 (1.154–2.14), P value = 0.004). Moreover, rs1799752 was associated with ASD in all assessed inheritance models (P values = 1.9E-28, 0.000005, 4.6E-18, 1.6E-8 and 3.2E-34 for co-dominant (II vs. DD), co-dominant (ID vs. DD), dominant, recessive and over-dominant models. ConclusionCumulatively, ACE gene might be regarded as a risk locus for ASD in Iranian population.

TAS1R3 and TAS2R38 Polymorphisms Affect Sweet Taste Perception: An Observational Study on Healthy and Obese Subjects.

Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.

Polymorphism of rs12294045 in EAAT2 gene is potentially associated with schizophrenia in Chinese Han population

BackgroundRecent studies have shown that the excitatory amino acid transporters (EAATs) are associated with schizophrenia. The aim of this study was to investigate the relationship between the polymorphism of EAAT1 and EAAT2 genes and schizophrenia in Chinese Han population.MethodsA total of 233 patients with schizophrenia and 342 healthy controls were enrolled. Two SNPs in EAAT1 gene (rs2269272, rs2731880) and four SNPs in EAAT2 gene (rs12360706, rs3088168, rs12294045, rs10836387) were genotyped by SNaPshot. Clinical features were collected using a self-made questionnaire. Psychotic symptoms of patients were measured by the Positive and Negative Syndrome Scale (PANSS), and patients’ cognitive function was assessed by Matrics Consensus Cognitive Battery (MCCB).ResultsSignificant difference in allelic distributions between cases and controls was confirmed at locus rs12294045 (Ρ = 0.004) of EAAT2 gene. Different genotypes of rs12294045 were associated with family history (P = 0.046), in which patients with CT genotype had higher proportion of family history of psychosis. The polymorphism of rs12294045 was related to working operational memory (LNS: P = 0.016) and verbal learning function (HVLT-R: P = 0.042) in patients in which CT genotype had lower scores. However, these differences were no longer significant after Bonferroni correction.ConclusionsOur study showed that the polymorphism of rs12294045 in EAAT2 gene may be associated with schizophrenia in Chinese Han population. CT genotype may be one of the risk factors for family history and cognitive deficits of patients.

Caffeine Therapy for Apnea of Prematurity: Role of the Circadian CLOCK Gene Polymorphism.

Standard-dose caffeine citrate has been routinely prescribed for apnea of prematurity (AOP) management; however, some preterm infants respond well to the therapy while others do not. The AOP phenotype has been attributed solely to the immature control of the respiratory system consequent to preterm birth, but there are also important genetic influences. Based on our previous report, we tested the hypothesis that the human circadian locomotor output cycles kaput (CLOCK) gene polymorphisms play a role in the response to caffeine citrate therapy in preterm infants. We also studied the interactions of the circadian clock with aryl hydrocarbon receptor (AHR) signaling pathways in preterm babies who received caffeine citrate. This single-center study collected data from 112 preterm infants (<35 weeks gestational age) between July 2017 and July 2018, including apnea-free (n = 48) and apneic (n = 64) groups. Eighty-eight candidate single nucleotide polymorphisms (SNPs) were tested using the MassARRAY system. Association analysis was performed using the PLINK Whole Genome Data Analysis Toolset and SNPStats software. Linkage disequilibrium (LD) and haplotype analyses were performed using Hapview software. No significant intergroup differences in allele distributions or genotype frequencies of CYP1A2, CYP3A4, CYP3A5, and CYP3A7 were detected in our study on preterm babies. Two more SNPs in AHR were found to be associated with determining the response to caffeine citrate therapy in our pediatric patients. Of the 46 candidate SNPs in the CLOCK gene, 26 were found to be associated with determining the response to caffeine treatment in these babies. Interestingly, a significant association was retained for 18 SNPs in the CLOCK gene after false discovery rate correction. Moreover, strong LD formed in those variants in AHR, ADORA2A, and CLOCK genes was confirmed to be significantly associated with a better response to standard-dose caffeine therapy. In summary, CLOCK gene polymorphisms play a role in determining the response to caffeine therapy in premature neonates with AOP. However, whether the AHR and CLOCK signaling pathways crosstalk with each other during caffeine treatment remains largely unclear. Future clinical studies including more immature babies and basic research are needed to explore the mechanism by which circadian rhythms affect the response to caffeine therapy.

SINGLE NUCLEOTIDE POLYMORPHISM RS4696480 OF TLR2 GENE ASSOCIATES WITH SEVERITY OF ATOPIC DERMATITIS IN CHILDREN, BUT NOT WITH IGE SENSITIZATION TO MALASSEZIA.

The aim: Malassezia has been linked to atopic dermatitis, and TLRs are suggested to mediate influence of Malassezia spp on human cells. The aim of the study was to examine if TLR2 rs4696480 polymorphism predisposes to atopic dermatitis, IgE sensitization to Malassezia or to severe phenotype of atopic dermatitis. Materials and methods: The study included 103 patients with eczema and 84 healthy children. Specific IgE against Malassezia mix (m227) was analyzed in 47 patients using immunochemiluminescent method on the ImmunoCAP 100 (Thermo Fisher Scientific Inc., Phadia, Sweden). Genotyping for TLR2 rs4696480 was performed by using Real-time PCR. Results: Increased IgE to Malassezia spp. was observed in 34,3 % of children with eczema. Higher Malassezia spp.-specific IgE titre positively correlated with duration of atopic dermatitis and a higher total IgE. There were no difference in allele distribution among patients and control group (OR=1.096 (0.549- 2.191) for AT, OR=0.946 (0.430- 2.078) for TT, р > 0,05). TLR2 polymorphism rs4696480 was not associated with Malassezia spp.-sIgE. AA-genotype was significantly more frequent among patients with severe and moderate-to-severe AD (OR=6.395 (1.240-32.991). Conclusions: AA variant of TLR2 rs4696480 polymorphism predisposes to severe phenotype of AD.

DIAPH2, PTPRD and HIC1 Gene Polymorphisms and Laryngeal Cancer Risk.

AIM, DIAPH2, PTPRD and HIC1 are the cell glycoprotein, which play an important role in the occurrence and development of tumors. This study was designed to assess the association between DIAPH2, PTPRD and HIC1 SNPs and laryngeal cancer risk. PATIENTS AND METHODS: This study including 267 patients with histologically confirmed laryngeal cancer and 157 controls. The relationship between genetic variations DIAPH2 (rs6620138), PTPRD (rs3765142) and HIC1 (rs9901806) and the onset of laryngeal cancer were investigated. Statistical analysis to calculate the relationship between DIAPH2, PTPRD and HIC1 genes polymorphism and pathogenesis of laryngeal cancer. RESULTS: The results showed that rs6620138 DIAPH2 polymorphism could increase the onset risk of laryngeal cancer. Statistically significant differences in allele distribution of rs6620138 DIAPH2 and rs9901806 HIC1 in the case and control groups subgroups. CONCLUSIONS: This study results suggested that genetic variation of rs6620138 DIAPH2 polymorphism is related to the susceptibility to laryngeal cancer. Our results provide a basis to begin basic research on the role of DIAPH2 gene in the pathogenesis of laryngeal cancer.

Intronic SNP - rs9288953 Of Suppressor Molecule Btla Confers Susceptibility To B-Cell Chronic Lymphocytic Leukemia

The contribution of the immune system to the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) have been receiving growing attention. The increase of cancer risk in immunodeficient individuals has been documented in population and experimental studies (Gurlich et al 2007; Swann et al 2007, Smyth et al 2006). A new member of co-inhibitory molecules B - and T-lymphocyte attenuator (BTLA) that inhibits lymphocyte activation could influence cancer susceptibility (Watanabe et al 2003). A high expression of BTLA was observed on malignant B cells from chronic lymphocytic leukemia/small lymphocytic leukemia (M'Hidi et al. 2009). As BTLA synthesis depends on the rate of gene transcription and/or translation, polymorphism in the corresponding gene might result in abnormal expression and function.The aim of this studywas to evaluate possible associations between selected on the basis of literature (Fu et al 2009) single nucleotide polymorphisms (SNPs) existing within exons and introns of BTLA gene: rs9288952A>G, rs1844089G>A, rs2705535C>T and 9288953C>T and susceptibility to B-CLL.Genotyping was done using allelic discrimination method with the TaqMan SNP Genotyping Assays in 300 B-CLL patients (pts.) (203 pts. from Department of Hematology, Medical University Lodz, Poland and 97 from Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Poland (138 female/162 male) and in 417 healthy individuals (168 female/243 male) originating from the same region of Poland.The significant differences in distribution of alleles and genotypes was observed for intronic SNP -rs9288953. The frequency of T allele and T alleles carriers (CT+TT genotypes) were higher in patients than in healthy controls as compare to C allele and CC genotypes (0.458 vs. 0.375, p=0.0016; OR:1.41, 95%CI - 1.13-1.75 and 0.677 vs. 0.606, p=0.0022; OR:1.67, 95%CI- 1.16-1.2.40, respectively). None of other investigated SNPs have shown different frequency of alleles or genotypes in group of patients and controls.The haplotype analysis of rs9288952A>G, rs1844089G>A, rs2705535C>T and 9288953C>T showed that the most common haplotypes rs9288952A>G[A]/rs1844089G>A[G]/rs2705535C>T[C]/ 9288953C>T[C] (named as AGCC) and rs9288952A>G[A]/rs1844089G>A[G]/rs2705535C>T[C]/ 9288953C>T[T] (named as AGCT) which were differentiate only by variants of 9288953C>T SNP were completely contrary associated with disease susceptibility. Haplotype AGCC is associated with decreased risk of B-CLL (OR: 0.72, 95%CI-0.59-0.90 p with Bonferroni correction=0.01), while AGCT with increased risk of disease (OR: 1.42, 95%CI-1.14-1.76 p with Bonferroni correction=0.005)Our data indicated for the first time the possible role of intronic polymorphism 9288953C>T in gene encoding suppressor molecule BTLA in susceptibility to B-CLL. ReferencesFu Z, Li D, Jiang W, Wang L, Zhang J, Xu F, Pang D, Li D. Association of BTLA gene polymorphisms with the risk of malignant breast cancer in Chinese women of Heilongjiang Province. Breast Cancer Res Treat. 2010 Feb;120(1):195-202.Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007 Jul 7;370(9581):59-67.M'Hidi H, Thibult ML, Chetaille B, Rey F, Bouadallah R, Nicollas R, Olive D, Xerri L. High expression of the inhibitory receptor BTLA in T-follicular helper cells and in B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia.Am J Clin Pathol. 2009 Oct;132(4):589-96.Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol. 2006;90:1-50.Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007 May;117(5):1137-46.Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, Hurchla MA, Zimmerman N, Sim J, Zang X, Murphy TL, Russell JH, Allison JP, Murphy KM. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.Nat Immunol. 2003 Jul;4(7):670-9. Disclosures:No relevant conflicts of interest to declare.

Study of cognitive impairment and genetic polymorphism of SLC41A1 (rs11240569 allele) in Parkinson\u2019s disease in Upper Egypt: case-control study

BackgroundParkinson’s disease is one of the neurodegenerative disorders that is caused by genetic and environmental factors or interaction between them. Solute carrier family 41 member 1 within the PARK16 locus has been reported to be associated with Parkinson’s disease. Cognitive impairment is one of the non-motor symptoms that is considered a challenge in Parkinson’s disease patients. This study aimed to investigate the association of rs11240569 polymorphism; a synonymous coding variant in SLC41A1 in Parkinson’s disease patients in addition to the assessment of cognitive impairment in those patients.ResultsIn a case -control study, rs11240569 single nucleotide polymorphisms in SLC41A1, genes were genotyped in 48 Parkinson’s disease patients and 48 controls. Motor and non-motor performance in Parkinson's disease patients were assessed by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The genotype and allele frequencies were compared between the two groups and revealed no significant differences between case and control groups for rs11240569 in SLC41A1 gene with P value .523 and .54, respectively. Cognition was evaluated and showed the mean ± standard deviation (SD) of WAIS score of PD patients 80.4 ± 9.13 and the range was from 61 to 105, in addition to MMSE that showed mean ± SD 21.96 ± 3.8.ConclusionGenetic testing of the present study showed that rs11240569 polymorphism of SLC41A1 gene has no significant differences in distributions of alleles and genotypes between cases and control group, in addition to cognitive impairment that is present in a large proportion of PD patients and in addition to the strong correlation between cognitive impairment and motor and non-motor symptoms progression.

CAT-21 A/T Gene Polymorphisms Associated with Breast Cancer Susceptibility

Background: Oxidative stress induced cancer cell formation. Gene polymorphism plays roles in carcinogen metabolism, antioxidant and DNA repairing pathway was susceptibility to oxidative stress. This study aim to determine the association between CAT-21 A/T polymorphism with breast cancer susceptibility.&#x0D; Methods: Case control study was conducted on 65 breast cancer patient and 65 healthy control group. The whole blood samples were isolated from 65 breast cancer patients in Haji Adam Malik General Hospital Medan and 65 healthy control group. The CAT-21A/T polymorphism was analyzed by PCR-RFLP procedure. PCR-RFLP product was electrophoresed and visualized in agarose 4%.&#x0D; Results:The AA CAT-21 genotype were lower in breast cancer (BC) than healthy control (HC) group (31/47.7% vs 40/61.5%), in the contrary AT+TT genotype was greater in BC than HC group (34/52.3% vs 25/38.5%) with (p=0.159, OR=1.755, CI=0.874–3.525). A allele CAT-21 were found lower in BC than HC group (89/68.5% vs 105/80.8%) then T allele were greater in BC than HC group (41/31.5% vs 25/19.2%) with (p=0.033, OR=1.935;CI=1.022-3.428).&#x0D; Conclusions: There was significant difference in allele distribution of CAT-21 A/T between case and control group but no in genotype distribution. In this population study showed that allele of CAT -21 A/T polymorphism could represent as a risk factor to breast cancer.&#x0D; Bangladesh J Medicine July 2021; 32(2) : 79-84

Analysis of gender-specific associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms and serum uric acid levels in Han Chinese.

BackgroundSerum uric acid (SUA) is influenced by lifestyle and genetics, and unbalanced SUA levels are linked to various common disorders. While the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism appears to be associated with SUA levels, the evidence remains inconclusive. The aim of this study was to examine the distribution of the ALDH2 rs671 polymorphism among Han Chinese in Beijing and determine the association between this polymorphism and SUA.MethodsA total of 6,461 randomized healthy individuals were included in the study. Biochemical indicators were tested and ALDH2 rs671 polymorphism testing was conducted for subjects enrolled in the study. The distribution of the ALDH2 rs671 polymorphism and the relationship between genotype and the levels of serum lipids and uric acid (UA) were analyzed.ResultsThe ALDH2 rs671 genotype frequencies were 68.1% (G/G), 29.3% (G/A), and 2.6% (A/A). There was no significant difference in allele distribution between males and females. In males, different ALDH2 genotypes exhibited significant differences in several biochemical analytes, including body mass index (BMI), blood glucose (Glu), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), UA, glutamyl transpeptidase (GGT), and creatinine (Cr) (P<0.05). No such differences were found in females. SUA levels in G/A and A/A-carrying males were significantly lower than those of G/G-carrying males. The effect of the ALDH2 polymorphism on UA was still significant after further adjustment for factors including BMI, Glu, TC, HDL-C, Cr, and GGT.ConclusionsThe ALDH2 polymorphism is related to SUA in Beijing males, and A allele-carrying males have lower SUA levels.

TOLL LIKE RECEPTOR-4 GENE ASPARTATE 299 GLYCINE POLYMORPHISM IN SUDANESE PATIENTS WITH MYCETOMA

Background: Mycetoma is a neglected tropical disease characterized by deformity and disabilities with various medical, health, and socioeconomic impacts on the affected communities. The etiological factors associated with Mycetoma have not been fully understood, however genetic predisposition and inflammation are considered as Mycetoma risk factors. Toll like receptors (TLRs) are key players in the innate immune response and play a great role in immune-surveillance and inflammation. This study was conducted to investigate the potential role of TLR4 polymorphism (Asp299Gly) as a risk factor for development of Mycetoma. &#x0D; Objectives: To determine the presence of TLR4 polymorphism (Asp299Gly) in Sudanese Mycetoma patients as well as measuring allele frequency and genotype distribution of this mutation among Mycetoma patients and healthy controls.&#x0D; Material and Methods: The current study included ninety five (95) subjects, of whom fifty (50) were confirmed Mycetoma patients and forty five (45) were healthy volunteer controls. It was conducted at the Institute of Endemic Diseases and Mycetoma Research Centre; University of Khartoum in the period, from June 2015 to June 2016. DNA was isolated from blood samples of study subjects and TLR-4 gene polymorphism Asp299Gly was determined using PCR-RFLP with Nco1 restriction enzyme. Genotypes distribution and allele frequencies in the two groups were measured.&#x0D; Results and conclusion: There was insignificant difference in allele distribution of TLR4 (Asp299Gly) A/G (rs 4986790) in Mycetoma patients compared with the healthy controls. TLR4 (Asp299Gly) polymorphism (rs 4986790) was found in twenty(20) out of fifty (50) Sudanese patients with Mycetoma , that is forty percent (40%) and twenty seven (27) out of forty five (45) healthy control, that is sixty percent (60%).&#x0D; Further studies are needed in a large and ethnically diverse population to determine the impact of the TLR-4 polymorphism in the susceptibility to Mycetoma.

Repeats expansions in ATXN2, NOP56, NIPA1 and ATXN1 are not associated with ALS in Africans.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized primarily by progressive loss of motor neurons. Although ALS occurs worldwide and the frequency and spectrum of identifiable genetic causes of disease varies across populations, very few studies have included African subjects. In addition to a hexanucleotide repeat expansion (RE) in C9orf72, the most common genetic cause of ALS in Europeans, REs in ATXN2, NIPA1 and ATXN1 have shown variable associations with ALS in Europeans. Intermediate range expansions in some of these genes (e.g. ATXN2) have been reported as potential risk factors, or phenotypic modifiers, of ALS. Pathogenic expansions in NOP56 cause spinocerebellar ataxia-36, which can present with prominent motor neuron degeneration. Here we compare REs in these genes in a cohort of Africans with ALS and population controls using whole genome sequencing data. Targeting genotyping of short tandem repeats at known loci within ATXN2, NIPA1, ATXN1 and NOP56 was performed using ExpansionHunter software in 105 Southern African (SA) patients with ALS. African population controls were from an in-house SA population control database (n = 25), the SA Human Genome Program (n = 24), the Simons Genome Diversity Project (n = 39) and the Illumina Polaris Diversity Cohort (IPDC) dataset (n = 50). We found intermediate RE alleles in ATXN2 (27–33 repeats) and ATXN1 (33–35 repeats), and NIPA1 long alleles (≥8 repeats) were rare in Africans, and not associated with ALS (p > 0.17). NOP56 showed no expanded alleles in either ALS or controls. We also compared the differences in allele distributions between the African and n = 50 European controls (from the IPDC). There was a statistical significant difference in the distribution of the REs in the ATXN1 between African and European controls (Chi-test p < 0.001), and NIPA1 showed proportionately more longer alleles (RE > 8) in Europeans vs. Africans (Fisher’s p = 0.016). The distribution of RE alleles in ATXN2 and NOP56 were similar amongst African and European controls. In conclusion, repeat expansions in ATXN2, NIPA1 and ATXN1, which showed associations with ALS in Europeans, were not replicated in Southern Africans with ALS.