Frequency Of TT Genotype Research Articles

Assessment of the Relationship Between ERBB4 rs13393577 Polymorphism and Breast Cancer Susceptibility in Iranian Population

Background: Studies have shown that the polymorphism of genes involved in breast cancer in combination with environmental factors has an important role in the progression of breast cancer. Objectives: In this study, the association between polymorphism of the ERBB4 gene with breast cancer was investigated. Methods: In the present study, 110 patients with breast cancer and 110 healthy individuals were selected as controls. DNA extraction was performed on patients’ samples. The tetra-ARMS-PCR method was used to study rs13393577 polymorphism. Finally, statistical analysis was performed using SPSS software using t-test. Results: The results of the study in the patients' group showed that the frequencies of TT, CT, and CC genotypes were 73, 15, and 1.8%, and allelic frequency in this group for T and C alleles were 95 and 5%, respectively. In addition, the results of the study in the control group showed that the frequencies of TT, CT, and CC genotypes were 86, 11, and 0.9%, respectively. The allelic frequencies in the control group for the T and C alleles were 97 and 3%, respectively. In addition, the risk ratio and allelic reliability were obtained for T allele was OR: 3.06: and CI = 0.31 – 29.94 and for C allele was OR: 0.32: and CI: 0.03 - 3.19, respectively. Finally, statistical analysis showed that no significant difference was observed between the two groups (P > 0.05). Conclusions: The results of the present study showed that rs13393577 polymorphism in the EGFR gene (ERBB4) is not a genetic predisposing factor for breast cancer.

Osteopontin Gene Polymorphisms rs1126616 C>T and rs1126772 A>G are Associated with Atopic Dermatitis in Polish Population.

PurposeAtopic dermatitis (AD) is a chronic, relapsing inflammatory disease, caused by environmental and genetic factors, which lead to immunological abnormalities. Osteopontin (OPN), also named secreted phosphoprotein 1 (SPP1), is a protein involved in the pathogenesis of numerous autoimmune and inflammatory conditions. However, its role in AD has not been fully elucidated. Therefore, we aim to gain an insight into the role of OPN in AD pathogenesis through investigating its gene single nucleotide polymorphisms (SNPs) and their possible associations with disease clinical features.Patients and MethodsA total of 182 Caucasian participants (45 AD patients and 137 gender- and age-matched controls) were studied. Genomic DNA was isolated from peripheral blood samples. Genotyping for the rs1126616 C>T, rs1126772 A>G, rs9138 A>C, and rs3841116 T>G SNPs was performed by real time polymerase chain reaction (RT-PCR).ResultsThe frequency of the minor TT genotype and the T allele of rs1126616 C>T was higher in AD patients compared to controls (P = 0.019, OD = 4.86, 95% CI = 1.46–16.20, and P = 0.047, OR = 1.77, 95% CI = 1.04–3.00, respectively) and was associated with the higher prevalence of asthma (P = 0.017, OR = 3.73, 95% CI = 0.71–19.67, and P = 0.004, OR = 3.96, 95% CI = 1.53–10.25, respectively). Likewise, the minor GG genotype and the G allele of rs1126772 A>G were more frequent in AD patients (P = 0.026, OR = 3.27, 95% CI = 1.29–8.33, and P = 0.013, OR = 1.94, 95% CI = 1.18–3.21, respectively) and were associated with the increased incidence of asthma (P = 0.016, OR = 5.06, 95% CI = 1.14–22.49, and P = 0.002, OR = 4.40, 95% CI = 1.71–11.35, respectively). Furthermore, haplotype frequency estimation determined the four-loci haplotype TGCT, as a significant risk factor for AD compared to controls (P = 0.031, OR = 9.48, 95% CI = 1.23–71.91).ConclusionOur results suggest that the variation in the OPN gene might be associated with AD and increased incidence of asthma in Caucasians. Further studies should be conducted to look into the possible role of OPN as a biomarker for AD.

MDR1 C3435T POLYMORPHISM: A PRELIMINARY STUDY ON ITS RELATIONSHIP WITH THE RISK OF COLORECTAL CANCER

Objective: Colorectal carcinoma (CRC) is the third most frequent cancer in the world and a heterogenious disease which aroze from one or a combination of different genetic mechanisms. The multiple drug resistance-1 (MDR1) gene which encodes P-glycoprotein (P-gp) plays a part in the bioavailability of drugs and cell toxicity. In the current study, we aimed to investigate the possible relation between the MDR1 gene C3435T polymorphism and CRC risk in the Turkish population. Material and Methods: Forty three patients (26 men, 17 women) with CRC and 48 healthy controls (34 men, 14 women) were included in the study. The MDR1 C3435T genotypes were determined by the Restriction Fragment Length Polymorphism (RFLP) method. Results: Statistical significance was obtained in terms of genotype distributions of MDR1 C3435T genotypes between study groups. The frequencies of MDR1 C3435T CC, TT and CT genotypes in the CRC patient group were found as 16.3%, 32.6% and 51.2%, respectively. The frequency of the homozygous TT genotype was found as 32.6% in CRC patients while it was identified as 14.6% in controls (p=0.04; OR=2.82, 95% CI: 1.01-7.87). When the patients were compared with the healthy population, TT genotype carriers of MDR1 C3435T polymorphism were found at 2.8-fold (p<0.05 ) increased risk for the development of CRC. Conclusion: Our results show that the MDR1 C3435T polymorphism might be one of the genetic risk factors for CRC development in the Turkish population.

Association between rs1344706 Polymorphism in the ZNF804A Gene and the Risk for Schizophrenia

Objective: Schizophrenia is known as a severe mental disorder worldwide. Genome-wide association studies have revealed that rs1344706, located in ZNF804A, is a risk variant for schizophrenia among various populations. The current study was conducted to find correlation between rs1344706 polymorphism and schizophrenia in East of Iran. Method: This case-control study assessed 150 schizophrenia cases as well as 150 healthy controls. The single nucleotide polymorphism (SNP) was genotyped using the Tetra-Amplification Refractory Mutation System-Polymerase Chain Reaction (Tetra-ARMS-PCR) method. Analyses based on the Chi-square test and logistic regression were calculated by SPSS. Results: The TT, GT, and GG genotype frequencies at rs1344706 in schizophrenia cases were 48.0%, 40.0%, and 12.0%, whereas in controls, they were 49.3 %, 36.7 %, and 14.0 %, respectively. The T and G allele frequencies were 68 % and 32 % in cases and 67 % and 33 % in healthy controls. The results of logistic regression indicated that there is no association between rs1344706 alleles (P = 1.000) and genotypes (P = 0.647 for GT and P = 0.726 for GG) with susceptibility to schizophrenia. Conclusion: Overall, there was no significant relationship between rs1344706 SNP and schizophrenia in Iran's Eastern population. However, further research focusing on more SNPs of ZNF804A and larger samples in other ethnicities is necessary to confirm these results.

C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case-Control and Meta-Analysis Study.

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn’s disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

C3435T Polymorphism of the ABCB1 gene in the Yakut Population

Background: The ABCB1 gene is responsible for resistance to various cytotoxic drugs. The product of the ABCB1 gene, P-glycoprotein (P-gp), acts as a transmembrane pump and influences the action of many drugs. More than 40 SNPs of the ABCB1 gene that alter the expression of P-gp have been identified. The ABCB1 rs1045642 SNP, designated as C3435T (C-the wild-type allele, T-the variant allele), correlates with the activity of P-gp. The aim of our research was to study the distribution of alleles and genotypes of the ABCB1 C3435T polymorphism in Yakuts, in comparison with other human populations. Methods and Results: The studied cohort included 149 healthy Yakut volunteers (36 men and 113 women). The average age of participants was 30.67±0.06 years. The ABCB1 gene is a highly polymorphic gene; the allele frequency of the C3435T polymorphism differs widely among the studied populations. The frequency of the mutant T-allele among the Yakuts was 51% .In the studied group of Yakuts, we revealed the prevalence of the heterozygous CT genotype (75.8%). The Yakuts have a relatively low frequency of CC (10.7%) and TT (13.4%) genotypes. This preliminary study did not include the objective of proving the relationship between the ABCB1 C3435T polymorphism and addictive disorders in Yakuts. The further search for functional polymorphisms of the ABCB1 gene and associations with addictive behavior using a systematic approach on larger samples is of great practical importance.

The association between fat mass and obesity-associated (FTO) genotype and serum vitamin D level in breast cancer patients.

The preventive effect of vitamin D against breast cancer can be influenced by gene polymorphisms. This study aimed to investigate the association between serum level of 25(OH) vitamin D and FTO genotype in breast cancer patients. A cross‐sectional study was carried out on 180 newly diagnosed patients with breast cancer in Tehran, Iran. The blood samples were collected from the participants in order to assess the FTO gene rs9939609 polymorphism by the tetra‐primer amplification refractory mutation system (Tetra‐ARMS) PCR method. The serum level of 25(OH) vitamin D was measured using the direct competitive enzyme‐linked immunosorbent assay (ELISA) method. The association between vitamin D and the FTO genotype in patients with breast cancer was assessed after adjustment for cofounders. The frequency of TT, AT and AA genotypes in the breast cancer patients were 43% (n = 77), 49% (n = 89) and 8% (n = 14), respectively. All patients with higher than 40 ng/dl of serum 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele (p = 0.019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer.

HDAC9 rs11984041 polymorphism is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes mellitus.

Histone deacetylase 9 (HDAC9) is an important regulator of transcription that has also been investigated as a candidate gene in some pathologies. Our aim was to investigate the association between rs2107595 and rs11984041 HDAC9 gene polymorphisms and diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated HDAC9 expression in the fibrovascular membranes (FVMs) of patients with proliferative DR (PDR). Our study involved 1290 unrelated Slovenian patients with T2DM: 542 of them with DR as the study group, and 748 without DR as the control group. The investigated polymorphisms were genotyped using KASPar genotyping assay. The expression of HDAC9 was examined by immunohistochemistry in human FVM from 25 patients with PDR. The T allele and TT genotype frequencies of the rs11984041 polymorphism were significantly higher in the study group compared to the controls. The logistic regression analysis showed that the carriers of the TT genotype of this polymorphism have a 3.76-fold increase (95% CI 1.04-11.67) in the risk of developing DR. The T allele of rs11984041 was associated with increased HDAC9 expression in FVMs, obtained from T2DM patients with PDR. Patients with the T allele of rs11984041 compared to the homozygotes for the wild type C allele exhibited higher density of HDAC9-positive cells (35±10/mm2 vs. 12±6/mm2, respectively). We observed a notable association between the TT genotype of rs11984041 and DR, indicating its possible role as a genetic risk factor for the development of this diabetic complication.

Evaluation of NOS2 Polymorphism in Gastric Adenocarcinoma Patients in Mazandaran Province

Introduction: Gastric cancer is the fourth most common cancer and the second leading cause of cancer death worldwide. North of Iran is a high-risk area for gastric cancer. Nitric oxide (NO), mainly synthesized by inducible nitric oxide synthase (NOS2) in pathological conditions, plays an important role in cytotoxicity, inflammation and fibrosis. In this research we studied the effect of (rs1137933) T>C genotype on gastric cancer. Methods: This analysis was performed on 93 patients with gastric cancer who were referred to endoscopy Tuba Clinic in 2015 and 93 healthy individuals as controls. DNA extracted from peripheral blood samples was applied in PCR-RFLP (Polymerase chain reaction- restriction fragment length polymorphism) analysis to determine (rs1137933) T>C genotype. The association of the (rs1137933) T>C genotype and gastric cancer risk were analyzed by MedCalc software and (X2) Chi-square and (OR) Odds Ratio exams. Results: Frequency of TT, CT, and CC genotypes in cases was 12.61, 51.35 and 36% and 38.7, 34.4, and 26.8% in the control group. Significant association was found between (rs1137933) T>C genotype with gastric cancer chance, P<0.05, OR=2/04, 95% CI (1/37 to 3/03). Conclusion: The results of the study show that the presence of CC+CT genotypes may increase the risk of gastric cancer. P < 0.0001, OR=4.37 (2.17 to 8.80).Therefore, investigating the (rs1137933) T>C single nucleotide polymorphism of NOS2 gene could be an appropriate molecular marker that could be used to determine individual sensitivity to gastric cancer and for designing cancer prevention programs.

ASSOCIATION OF CD14 (C-159T) GENE POLYMORPHISM AND IRRITATED INTESTINE SYNDROME WITH OBESITY

The purpose of the study – to study the association of the polymorphic variant C-159Tof the CD14 gene in patients with irritable bowel syndrome (IBS) depending on thepredominance of diarrhea or constipation in the clinical course and the relationshipbetween genotypes of the CD14 gene (C-159T) and some blood parameters.Material and methods. The study involved 90 patients with IBS (30 men and 60women aged 22 to 56 years). The polymorphic variant of the CD 14 gene (C-159T)was analyzed by polymerase chain reaction in 90 patients with IBS without and withconcomitant obesity and 30 people in the comparison group. Blood levels of C-reactiveprotein (CRP), tumor necrosis factor α (TNFα), transforming growth factor β1(TGFβ1), interleukin-10 (IL-10), 8-isoprostane, ceruloplasmin, medium molecules andcalprotectin levels in feces were determined.Results. In patients with IBS and obesity, the frequency of TT genotype (36.7%) washigher compared to healthy subjects (TT genotype – 13.3%). Significantly higherserum levels of CRP (3.5 times and 26.7%), TNFα (1.7 times and 19.5%), TGFβ1(29.8% and 19.2%), 8-isoprostane (54.1% and 31.9%), ceruloplasmin (56.7% and33.0%), medium molecules (7, 5% and 12.9%) and calprotectin (55.7% and 37.4%) inthe feces compared to the CC and CT genotype have been determined in patients withIBS, combined with obesity, TT genotype with a predominance of diarrhea.Conclusions. The association of a polymorphic variant of the CD14 (C-159T) gene withthe risk of IBS development in obese patients has been established. The TT genotype ischaracterized by a higher content of proinflammatory cytokines (TNFα), lower levelsof anti-inflammatory cytokines (IL-10), increased CRP, more pronounced changesin the prooxidant and antioxidant blood systems (higher levels of 8-isoprostane andceruloplasmin, local inflammation (increase in calprotectin content) and severity ofendotoxicosis (higher content of medium molecules).

Association between the PLTP rs4810479 SNP and Serum Lipid Traits in the Chinese Maonan and Han Populations

The association between the phospholipid transfer protein (PLTP) gene rs4810479 single-nucleotide polymorphism (SNP) and serum lipid levels is largely unknown. This investigation aimed to evaluate the relationship between the PLTP rs4810479 SNP, several environmental risk factors, and serum lipid parameters in the Chinese Maonan and Han nationalities. Polymerase chain reaction-restriction fragment length polymorphism, gel electrophoresis, and direct sequencing were employed to determine the PLTP rs4810479 genotypes in 633 Maonan and 646 Han participants. The frequencies of CC, CT, and TT genotypes and the C allele were different between Maonan and Han groups (29.07%, 53.08%, 17.85%, and 55.61% vs. 35.60%, 49.70%, 14.70%, and 60.45%, respectively, P < 0.05). The C allele carriers in the Maonan group had higher high-density lipoprotein cholesterol levels than the C allele noncarriers, but this finding was only found in Maonan males but not in females. The C allele carriers in Han males had lower total cholesterol and low-density lipoprotein cholesterol levels than the C allele noncarriers. Serum lipid profiles were also affected by several traditional cardiovascular risk factors in both populations. There might be an ethnic- and/or sex-specific association between the PLTP rs4810479 SNP and serum lipid traits.

The associations between THBD c.1418C>T polymorphism and lower extremity deep vein thrombosis or endothelial progenitor cell.

Studies have shown that the thrombomodulin gene (THBD) c.1418C>T polymorphism is associated with a variety of cardiovascular diseases. However, the study of THBD c.1418C>T polymorphism in deep vein thrombosis (DVT) is rare. This study aimed to reveal the correlation between the THBD c.1418C>T mutation and the occurrence of DVT, and to reveal partial molecular mechanism of endothelial progenitor cells (EPCs) participating in the onset of DVT. Whole blood samples of patients with lower extremity DVT (N.=100) and normal volunteers (N.=100) were collected to analyze the distribution of genotype of THBD c.1418C>T polymorphism using PCR and DNA sequencing. The pCMV6-entry vectors containing wild-type (WT) or mutated THBD cDNA (p. Ala473Val) were transfected into bone marrow derived EPCs. And the successful transfection of recombinant THBD and the stable expression of p. Ala473Val variant were determined by ELISA, respectively. Wound healing assay and Transwell migration assay were used to determine the migration ability of EPCs, and the cell angiogenesis ability was determined by tube formation assay. Western blotting was used to detect the expression level of related proteins. The frequencies of CC, CT and TT genotypes were 56%, 36%, 8% in patients with lower extremity DVT and 72%, 25%, 3% in controls group, respectively, and THBD c.1418C>T polymorphism was related with increased risk of DVT, especially in women. High level of p. Ala473Val variant inhibited the EPCs migration, the p. Ala473Val variant significantly decreased the activation of protein C and the expressions of VEGFRs and MMP1, MMP2, MMP3. Furthermore, p. Ala473Val variant also weaken the angiogenesis of EPCs and decreased the expression level of VE-cadherin, Flk-1, eNOS, and TIE-2. THBD c.1418C>T polymorphism is related with the lower extremity DVT, this may partially because of the inhibition of migration and angiogenesis of EPCs.

Lack of Association between CYP1A1 3801T &amp;gt; C Polymorphism and Idiopathic Male Infertility in Algerian Population

&lt;p&gt;&lt;strong&gt;Background and Objective:&lt;/strong&gt; Ongoing research suggests that cytochrome P4501A1 (CYP1A1) 3801T &amp;gt; C polymorphism may be correlated with human male infertility but the reported results are conflicting. Hence, this case-control study was conducted in Algerian population to determine the frequency of this polymorphism and its relationship to male infertility.&lt;br /&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This study included 173 subjects grouped into two categories: controls (84) and patients (89) with abnormal semen analysis parameters. Genomic DNA from the patients and controls was extracted and PCR-restriction fragment length polymorphism was used to genotype the 3801T &amp;gt; C CYP1A1 polymorphism.&lt;br /&gt;&lt;strong&gt;Results:&lt;/strong&gt; In the control group, the frequency of homozygous wild-type TT, heterozygous TC, and mutant homozygous CC genotypes of the CYP1A1 T &amp;gt; C polymorphism was 84.52%, 13.10%, and 2.38%, respectively, while infertile men had 77.53%, 20.22%, and 2.25%, respectively. There was no correlation between the 3801T &amp;gt; C CYP1A1 variant and male infertility. Furthermore, the rs4646903 C allele was not a risk factor in the dominant genetic model.&lt;br /&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; The 3801T &amp;gt; C polymorphism cannot be considered as a risk factor for male infertility in Algerian population. Our results need to be validated and confirmed through prospective studies with a larger number of patients.&lt;/p&gt;&#x0D; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

CCR4 1014C/T and CCL22 16C/A Genetic Variations in the Iranian Patients with Thyroid Cancer

Background: The aim of this study was to investigate the association between thyroid cancer and 16C/A single nucleotide polymorphism (SNP) in C-C motif chemokine 22 (CCL22) as well as 1014C/T SNP in C-C chemokine receptor type 4 (CCR4). Method: In this case-control study, Polymerase Chain Reaction Restriction-Fragment Length Polymorphism (PCR-RFLP) was performed for 113 thyroid cancer patients and 112 age-sex matched healthy controls to investigate the genotype distribution. Results: At position 16C/A in CCL22, 95 patients (84.3%) were found to have CC genotype while 17 individuals (14.8%) inherited CA genotype and 1 (0.9%) had AA genotype. In the control group, 92 volunteers (82.1%) inherited CC genotype, 18 individuals (16.1%) had CA genotype, and 2 (1.8%) had AA genotype. The frequency of CC, CT, and TT genotypes of 1014C/T SNP in CCR4 gene was 60 (53.1%), 43 (38.1%), and 10 (8.8%) in the patients, and 57 (53.3%), 43 (40.2%), and 7 (6.5%) in the control group, respectively. There were no statistically significant differences between the patients and controls in terms of 16C/A polymorphism in CCL22 (P= 0.816) and 1014C/T SNP in CCR4 1014C/T gene position (P=0.801). Nevertheless, the study of their association indicated that inheriting the CC genotype of CCR4 is significantly associated with higher stages (stages 3 and 4) in thyroid cancer. Conclusion: 1014C/T genetic variation in CCR4 and 16C/A polymorphism in CCL22 were not found to have a role in the incidence of thyroid cancer. Inheriting CC genotype at 1014 locus in CCR4 may, however, affect cancer progression in patients with thyroid cancer.

Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study.

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

Relationship between IKZF3 Gene Single Nucleotide Polymorphisms and Childhood Acute Lymphoblastic Leukemia

To investigate the relationship between single nucleotide polymorphisms (SNPs) of IKAROS family Zinc finger 3 (IKZF3) gene and the risk of acute lymphoblastic leukemia (ALL) in children. The peripheral blood samples from 286 children with ALL and 382 healthy children were collected and divided into ALL group and control group, respectively. The genotypes of IKZF3 gene at rs62066988 C > T and rs12946510 C > T were detected by quantitative PCR with TaqMan detection system, and their correlation with ALL was analyzed. The distribution frequencies of CC, CT and TT genotypes at rs62066988 in ALL group were 58.39%, 37.06% and 4.55%, respectively, while those in control group were 69.19%, 27.68% and 3.13%, respectively. The distribution frequencies of CC, CT and TT genotypes at rs12946510 in ALL group were 58.16%, 34.75% and 7.09%, respectively, while those in control group were 55.76%, 37.43% and 6.81%, respectively. Compared with the control group, the distribution frequency of CT/TT genotype at rs62066988 was significantly increased in the ALL group (OR=1.59, 95%CI: 1.16-2.19, P=0.004). However, there was no significant difference in the distribution of rs12946510 C > T polymorphism between ALL group and control group. The CT/TT genotype of IKZF3 at the site of rs62066988 is associated with the increased risk of ALL in children.

Association of −819 T/C IL-10 gene promoter polymorphisms with susceptibility to leprosy in South Sumatera Indonesia

Background: The prevalence of leprosy continues to increase, especially in Indonesia, which is one of the endemic areas of leprosy. One cytokine that plays an important role in the pathogenesis of leprosy is IL-10. Mutations in the gene could cause changes in IL-10 gene expression. One of the most common polymorphisms associated with the IL-10 gene is −819 C/T polymorphism, which is could affect the production of IL-10, and thus influence the process of microbial elimination in the development of leprosy. Objective: To determine the association of −819 C/T interleukin-10 promoter gene polymorphism in leprosy patients treated at RSUP Dr. Mohammad Hoesin Palembang. Method: This study was an analytic observational study with a case–control design. Blood from patients who fulfilled the inclusion criteria was taken through venous puncture and stored in EDTA tubes. DNA isolation was carried out with a DNA blood mini kit (QIAamp) and stored at −20 °C. Polymorphism of −819 C/T interleukin-10 promoter gene was measured by PCR-RFLP method, electrophoresis, and visualized under UV light. Results: In the case group, TT genotype frequency distribution was 21%, CT was 22%, and CC was 7%. In the control group, TT genotype frequency distribution was 28%, CT was 18%, and CC was 4%. In the case group, the allele T frequency distribution was 32% and C allele was 18%. In the control group, the T allele frequency distribution was 37% and C allele was 13%. Conclusion: There is no significant association of −819 C/T Interleukin-10 promoter gene polymorphism with susceptibility to leprosy, both in terms of genotypes and alleles of these genes.

Mutant Single Nucleotide Polymorphism rs189037 in Ataxia-Telangiectasia Mutated Gene Is Significantly Associated With Ventricular Wall Thickness and Human Lifespan.

In the current study, we aimed to determine the association of single nucleotide polymorphism rs189037 in ataxia-telangiectasia mutated (ATM) gene with cardiac structure and human longevity. Based on the China Hainan Centenarian Cohort Study performed in 18 cities and counties of Hainan Province, China, the current study enrolled 547 centenarians, 250 young participants aged 20–45 years, and 250 middle-aged and elderly participants aged 46–90 years. The frequency of TT genotype was significantly higher and that of CC genotype was significantly lower in middle-aged and elderly participants than in young (P = 0.012) and centenarian (P = 0.041) participants. There were no significant differences in the genotype and allele frequencies of SNP rs189037 between young and centenarian participants. Compared with CT genotype, TT genotype was positively and significantly associated with interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in centenarian (IVST: P = 0.049; LVPWT: P = 0.047) and middle-aged and elderly (IVST: P = 0.008; LVPWT: P = 0.004) participants. Compared with CC genotype, TT genotype was positively and significantly associated with LVPWT in centenarian (P = 0.030) and middle-aged and elderly (P = 0.013) participants. Compared with CC genotype, CT genotype was negatively and significantly associated with left ventricular end-diastolic diameter (LVEDD) in centenarian (P = 0.011) and middle-aged and elderly (P = 0.040) participants. The current study demonstrated that mutant rs189037 in the ATM gene was more commonly identified in middle-aged and elderly participants than in young and centenarian participants, was significantly associated with increased left ventricular wall thickness and volume, and could induce left ventricular eccentric hypertrophy and shorten human lifespan. Therefore, rs189037 without mutation might be an indicator of youth health and successful aging, whereas mutant rs189037 might hinder human longevity.

Significant Association of Polymorphisms in the TCF7L2 Gene with a Higher Risk of Type 2 Diabetes in a Moroccan Population.

Background and aims: Several studies have shown that genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) are highly associated with the development of type 2 diabetes mellitus (T2DM) and its associated complications in several populations. The aim of our study was to investigate the association of the rs7903146 (C/T) and rs12255372 (G/T) polymorphism in the TCF7L2 gene with the risk of developing T2DM in the Moroccan population. Material and methods: A total of 150 T2DM patients and 100 healthy controls were recruited for various anthropometric, biochemical and genetic parameters. Genotyping was performed by using Real Time-PCR. The frequency of genotypes, alleles, anthropometric measures, glycemia, glycated hemoglobin (HbA1c) were evaluated in patients and control, while lipid profile was available only for T2DM group. Results: Glycemia, HbA1c and body mass index (BMI) were significantly higher in T2DM group than control. Analysis of the distribution of the TCF7L2 rs7903146 genotype and allele revealed that the TT genotype was more frequent in T2DM group (24.0%) than in healthy controls (5%) (OR = 4.08, 95% confidence interval (CI = 1.95–11.80, p < 0.0001). The T allele was more frequent in diabetic patients (45.2%) than healthy control (34.5%) and it was associated with high risk of diabetes (OR = 2.13, 95% CI = 1.12–7.31, p = 0.005). The same results were found regarding rs12255372, TT genotype frequencies were 18,7% and 6.0% in T2DM and control group, respectively (OR = 3.11, 95% CI = 1.33–7.24, p = 0.004). The T allele was over-presented in diabetics compared to controls (45.3% and 38.0%, respectively) and increases the risk of T2DM (OR = 2.01, 95% CI = 1.04–3.10, p = 0.01). However, there was no significant difference between the three genotypes of rs7903146 and rs12255372 regarding age, BMI, glycemia, HbA1c and lipid profile. Conclusion: The present study confirmed a significant association of the TCF7L2 gene (rs7903146 (C/T) and rs12255372 (G/T) polymorphisms with a higher risk to T2DM in the Moroccan population. No significant difference in respect to anthropometric and metabolic parameters between different genotypes.

VAV1 Gene Polymorphism is Associated With Kidney Allograft Rejection

VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells. Several studies suggest that VAV1 signaling plays significant roles in allograft rejection. The aim of this study was to examine the association between VAV1 gene polymorphisms and renal allograft function. The study included 270 patients after allograft renal transplantation. We examined the associations between VAV1 gene polymorphisms and complications after transplantation, such as delayed graft function, acute rejection, and chronic allograft dysfunction. There were no statistically significant associations between VAV1 genotypes and delayed graft function and chronic allograft dysfunction. Among patients with acute allograft rejection, we observed decreased frequencies of VAV1 rs2546133 TT and CT genotypes (P=.03) and T allele (P=.02), as well as VAV1 rs2617822 GG and AG genotypes (P=.05) and G allele (P=0.04). In the multivariate regression analysis, the higher number of VAV1 rs2546133 T alleles showed a protective effect against the acute rejection in kidney allograft recipients. The results of our study suggest that polymorphisms in the VAV1 gene are associated with kidney allograft rejection.