Gene Promoter Polymorphism Research Articles

Evaluating of solute carrier family 6 member 4 gene (SLC6A4) promoter polymorphisms with escitalopram plasma levels for precision medicine in major depressive disorder

Aim and Objective: Escitalopram (SCT) shows an antidepressant effect due to its mechanism of increasing the serotonin level by inhibiting the serotonin transporter protein (5HTT). 5HTT is encoded by solute carrier family 6 member 4 gene (SLC6A4) in the brain. Recognition of SCT plasma level of patients and pharmacodynamics of individuals during SCT treatment will increase the expected response to the treatment and reduce the adverse effects. This study aims to determine the effect of SLC6A4 promoter long/short polymorphism and the SCT plasma level of patients on the response to treatment during the SCT drug therapy. Materials and Methods: Blood and plasma samples of 30 major depressive patients using 20 mg SCT for 8 weeks between the ages of 18 and 65 were analyzed to determine SCT plasma level and SLC6A4 promoter polymorphism. The treatment response level was determined by using the Hamilton Depression Rating Scale at patient files. Results: SCT plasma level of the nine patients with LL polymorphism was found to be in the range of 13.40–63.36 ng/mL. For 13 patients with LS polymorphism, SCT plasma level was found to be in the range of 2.93–57.48 ng/mL. For eight patients with SS polymorphism, the SCT plasma level was found to be in the range of 0.95–49.32 ng/mL. Conclusion: When the association between SCT plasma level and response to the drug treatment was examined, we had significant results to show that SCT level affected the response to treatment, especially in the LS group, as well as the SLC6A4 promoter variation. This study may lead to a more profound understanding of rational drug therapy as well as to a careful application of pharmacogenetics in psychiatry..

Association of IL-10 gene promoter polymorphisms with food allergy susceptibility and serum IL-10 level in a pediatric Caucasian population.

Interleukin 10 has been shown to play a critical role in the regulation of the immune responses in allergic diseases. To investigate if genetic polymorphisms in the promoter region of the IL-10 gene are associated with food allergy (FA) susceptibility in Caucasian pediatric patients with concomitant allergic diseases and IL-10 levels. The single nucleotide polymorphisms (SNPs) at -1082A>G (rs1800896), -819T>C (rs1800871), and -592A>C (rs1800872) of 62 pediatric patients with IgE-mediated FA were analyzed and correlated with clinical parameters, serum IgE and IL-10 levels. The results were compared with those of 92 healthy controls without FA, personal and/or family history of atopy. Analysis and comparison of genotype distributions, allele frequencies, and haplotypes showed that none of the genotypes confers an increased risk of FA. The genotype -1082 AA in FA patients was associated with moderate to severe symptoms of FA, the development of atopic asthma, and higher levels of IL-10. In a linear regression study, we confirmed that the genotype -1082 AA acts as an independent factor for the higher levels of IL-10. A positive association was also observed between -819T/C and -592 A/C SNPs and later onset of FA. Polymorphisms in the promoter region of the IL-10 gene are not associated with FA susceptibility in our cohort. In FA patients, -1082 A/G SNPs seem to influence the production of IL-10, the severity of FA symptoms, and the development of atopic asthma in this population.

Polymorphism of the Klotho G-395a Gene Promoter with the Incidence of Preeclampsia

A B S T R A C TIntroduction. Preeclampsia is one of the leading causes of maternal and perinatalmorbidity and mortality and is still a disease of theory. Klotho is a new gene, inseveral biological processes in the pathophysiology of preeclampsia that play a rolein regulating endothelial nitric oxide production, angiogenesis, production ofantioxidant enzymes and protection against endothelial dysfunction. The Klotho G-395A genotype AA promoter polymorphism is the cause of hypertension. This studyaims to determine the relationship of the Klotho G-395A promoter polymorphism tothe incidence of preeclampsia. Methods. This study is an analytical study with acase-control design. The research was conducted at Pembina community healthcentre of Palembang and the public hospital of Prabumulih in February - July 2020and involving 50 case group and 50 control group. To determine the genotype andallotype of the Klotho G-395A gene promoter polymorphism, using polymerase chainreaction examination. Result. The results showed that the risk factors for maternalage and maternal gestational age had a significant relationship with the incidence ofpreeclampsia (p-value 0.015; p-value 0.000). There was a significant relationshipbetween the Klotho G-395A genotype GA + AA promoter polymorphism and theincidence of preeclampsia (p-value 0.024; OR = 2.571; 95% CI = 1.122-5.895), whileallotypes in the study sample also had a significant relationship with the incidenceof preeclampsia. preeclampsia (p-value 0.025; OR = 1.978; 95% CI = 1.087-3.599).Conclusion: There is a significant relationship between the Klotho G-395A genepromoter polymorphism and the incidence of preeclampsia.

THE ROLE OF INTERLEUKIN-4 GENE PROMOTER POLYMORPHISMS IN GRAVES’ DISEASE

Objective: This study was conducted to prove the role of interleukin-4 gene promoter polymorphisms in Graves’ disease patients in M Djamil General Hospital Padang, Indonesia.
 Methods: This study was conducted from August 2015 until December 2015 in the Internal Medicine Department in Dr. M. Djamil Hospital, Padang, West Sumatera, Indonesia. This study involved 15 patients with Graves’ disease and 15 normal subjects. We examined that IL-4 promoter gene polymorphism was examined with PCR.
 Results: Sequencing examination on IL-4 gene promoter resulted in 2 Single Nucleotide Polymorphism (SNP) motifs, which is rs2243250 and rs2070847. IL-4 SNP gene promoter polymorphisms rs2243250 and rs2070847 were found in both patient and control groups. TT is homozygous SNP polymorphisms. CT is heterozygous SNP polymorphisms. CC is wild type or no mutation SNP polymorphisms. Based on statistical tests, no difference in rs2243250 and rs2070847 SNP polymorphisms was found between patient and control group (p > 0.05).
 Conclusion: This study observed no difference in interleukin-4 gene promoter polymorphism between Graves’ disease patients and control group.

Matrix metalloproteainase-3 polymorphism association with hypertrophic cardiomyopathy

Abstract Background Matrix metalloproteinase-3 (MMP-3) level disequilibrium in hypertrophic cardiomyopathy (HCM) may be due to a specific genetic variation. The MMP-3 gene promoter contains an insertion/deletion polymorphism characterized by an array of 5 or 6 adenosine residues (5A/6A) at –1612 positions. Purpose The aim was to analyze whether the MMP-3 5A/6A gene promoter polymorphism is related to its level in HCM patients. Methods/Results In this study, we recruited 33 HCM patients and 35 non-HCM. The ELISA sandwich assay measured MMP-3 plasmatic level. The MMP-3 –1612 5A/6A polymorphism was genotyped by RFLP-PCR. The studied population was consistentin Hardy-Weinberg equilibrium. There were 17% 5A/5A homozygotes, 65% 6A/6A homozygotes, and 17% 5A/6A heterozygotes. The HCM was related to the existence of the –1612 5A/6A polymorphism (p<0.05). Patients carrying the 5A allele had a higher MMP-3 level than those with the 6A allele (16.03±9.43 vs 8.68±5.89 ng/ml, respectively; p=0.01). Conclusion Our data shows that the –1612 5A/6A MMP-3 gene polymorphism is associated to the hypertrophic cardiomyopathy and do influence the MMP-3 plasmatic circulating level. Funding Acknowledgement Type of funding source: None

Correlation between Interleukin-4 Gene Promoter Polymorphisms with Thyrotropin Receptor Antibody and Transforming Growth Factor-β

AIM: The aim of this study was to determine the correlation between interleukin-4 (IL-4) gene promoter polymorphisms with thyrotropin receptor antibody (TRAb) and transforming growth factor-β (TGF-β).
 METHODS: This study was conducted from August 2015 until December 2015 in the internal medicine department in Dr. M. Djamil Hospital, Padang, West Sumatera, Indonesia. Graves’ disease was confirmed by measuring free thyroxine, thyroid-stimulating hormone, and TRAb. We examined that IL-4 promotor gene polymorphism was examined with a polymerase chain reaction. Graves’ disease serum patients will be used to check levels of TGFβ and TRAb antibodies using the enzyme-linked immunoassay method.
 RESULTS: There are 15 patients in this study. The average of age in patients group is 40.87 (11.23) years. The number of female patients in this study is more than male patients, with the percentage of women are 73.3%, and men are 26.7%. The sequencing examination on IL-4 gene promoter resulted in 2 single nucleotide polymorphism motifs, which are rs2243250 and rs2070847. The mean TRAb level in wild type and mutant group is 6.77 (5.73) IU/L and 4.66 (3.91) IU/L, respectively. The mean TGF-β levels in wild type and mutant group are 1168.89 (438.91) pg/mL and 1114.79 (296.02) pg/mL, respectively. Statistical tests showed no association between IL-4 gene promoter polymorphisms with TRAb and TGF-β levels (p > 0.05).
 CONCLUSION: There is no correlation between IL-4 gene promoter polymorphisms with TRAb and TGF-β.

High Level of Serum Cholesteryl Ester Transfer Protein and Chemerin as a Risk Factor of Metabolic Syndrome in Adolescent Obese and the Description of Cholesteryl Ester Transfer Protein −629c/A Gene Promoter Polymorphism

BACKGROUND: The prevalence of metabolic syndrome (MS) in children and adolescents has increased, along with increasing incidence of obesity.
 AIM: The aim of this study was to find out the polymorphism characteristic of cholesteryl ester transfer protein (CETP) -629C/A gene promoter and to prove that the CETP -629C/A polymorphism, serum CETP, and chemerin levels were risk factors of MS in obese adolescents.
 MATERIALS AND METHODS: A matched case–control study with obese adolescent aged 11–18 years was conducted from May to December 2017. Samples were consecutively recruited in seven junior and senior high schools in Denpasar. Case groups were obese adolescents with MS and control groups were obese adolescents without MS (non-MS obese). Both groups fulfilled eligibility criteria were matched by gender and puberty status. The study data were analyzed by Chi-square test and logistic regression with significant level p < 0.05.
 RESULTS: Analysis of CETP -629C/A polymorphism showed, AA and CA genotype were not a risk factors for MS when compared with CC genotype (OR = 0.81 [95% CI 0.23–2.88], p = 0.75 and OR = 0.95 [95% CI 0.38–2.37] p = 0.91, respectively). There was no significant difference between individual carriers A allele with individual carriers C allele to risk of MS (OR = 0.91 [95% CI 0.39–2.14], p = 0.83). The cutoff point of CETP levels was ≥2 μg/mL considered as CETP high levels, and <2 μg/mL considered normal; chemerin levels ≥170 ηg/mL considered as chemerin high levels, and <170 ηg/mL considered as normal. High levels of serum CETP were a risk factor in MS compared to normal levels (OR = 2.82 [95% CI 1.07–7.41], p = 0.036) and high levels of serum chemerin were a risk factor in MS compared to normal level (OR = 2.77 [95% CI 1.04–7.40], p = 0.042).
 CONCLUSION: This study concluded that high levels of serum CETP and chemerin were the risk factors for MS, while genotype AA CETP -629C/A gene polymorphism was not a risk factor for MS.

Relation of Uridine Diphosphate Glucuronosyltransferase 1A1 Promoter Gene Polymorphism (211G>A) With Risk of Hyperbilirubinemia in Neonates

Background: The gene 211G>A variants, that underlie complex disorders, are characteristically common in the neonatal hyperbilirubinemia. However, it is the contribution of multiple different co-expressed susceptibility genes that individually confer a small increase in risk coupled with environmental factors that generate complex disorder phenotypes. Objective: This study aimed to understand the relation of 211G>A promoter polymorphism in UGT1A1 gene and the risk of hyperbilirubinemia in newborns. Patients and Methods: The study included 50 newborns with hyperbilirubinemia with gestation age of ≥ 37weeks and postnatal age of ≤ 2 weeks with normal birth weight. 34 were males and 16 were females. They were divided into two groups; case group consisting of 30 neonates with the peak of total serum bilirubin (TSB) levels ≥ 16 mg /dl and control group consisting of 20 neonates with the peak total serum bilirubin (TSB) levels A genotype can be used as a novel method to detect susceptibility to indirect hyperbilirubinemia in neonates. Conclusion: Our findings added to the understanding of the significance of UGT1A1 in association with neonatal hyperbilirubinemia in East Delta of Egyptian population. Additionally we are in need for other studies to investigate the protective mechanisms.

Relation of Uridine Diphosphate Glucuronosyltransferase 1A1 Promoter Gene Polymorphism (211G>A) With Risk of Hyperbilirubinemia in Neonates

Background: The gene 211G>A variants, that underlie complex disorders, are characteristically common in the neonatal hyperbilirubinemia. However, it is the contribution of multiple different co-expressed susceptibility genes that individually confer a small increase in risk coupled with environmental factors that generate complex disorder phenotypes. Objective: This study aimed to understand the relation of 211G>A promoter polymorphism in UGT1A1 gene and the risk of hyperbilirubinemia in newborns. Patients and Methods: The study included 50 newborns with hyperbilirubinemia with gestation age of ≥ 37weeks and postnatal age of ≤ 2 weeks with normal birth weight. 34 were males and 16 were females. They were divided into two groups; case group consisting of 30 neonates with the peak of total serum bilirubin (TSB) levels ≥ 16 mg /dl and control group consisting of 20 neonates with the peak total serum bilirubin (TSB) levels A genotype can be used as a novel method to detect susceptibility to indirect hyperbilirubinemia in neonates. Conclusion: Our findings added to the understanding of the significance of UGT1A1 in association with neonatal hyperbilirubinemia in East Delta of Egyptian population. Additionally we are in need for other studies to investigate the protective mechanisms.

Association of genetic polymorphism at tumor necrosis factor-α gene promoter - 1031T/C and parasitic infections among children in Northern South Africa

Intestinal parasitic diseases are common in developing countries including South Africa and have been documented to be the most common in children under the age of five. The present study aimed to identify any potential association that may exist between TNF-α promoter gene polymorphism and parasitic infections. A total of 199 blood samples were evaluated from children who were part of the MAL-ED study cohort. The DNA was used to investigate polymorphism in the promoter region of the TNF-α gene at position -1031T/C. The polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. The TC genotype at position -1031 was significantly higher in healthy controls children than in children who were infected with Entamoeba species (59.9% vs 29.4%, P = 0.015) and Entamoeba coli (59.1% vs 30.8%, P = 0.046), indicating that TC genotype may be protective against Entamoeba infections and Entamoeba coli infections. The CC genotype at position -1031 was more common among children with parasite and diarrhea and the results was statistically significant (P = 0.04). This study has revealed that the CC genotype may be is a risk factor for symptomatic parasitic infections while the TC genotype might be protective of Entamoeba infections among children in Dzimauli community.

Association of Tumor Necrosis Factor Receptor 1 Promoter Gene Polymorphisms (-580 A/G and -609 G/T) and TNFR1 Serum Levels with the Susceptibility to Gastric Precancerous Lesions and Gastric Cancer Related to H. pylori Infection in a Moroccan Population.

Chronic inflammation due to H. pylori infection is the risk factor of gastric cancer (GC). Through its receptor (TNFR1), TNF-α plays a fundamental role in inflammatory, infectious, and tumor processes. Dysregulation of TNFR1 gene expression could impact many biological processes that can lead to cancer. This study is aimed at evaluating the association of TNFR1 promoter gene polymorphisms (-580 A/G and -609 G/T) and TNFR1 serum levels with GC and precancerous lesion susceptibility. Patients suffering from gastric lesions (65 chronic gastritis, 50 precancerous lesions, and 40 GC) related to H. pylori infection and 63 healthy controls (HC) were involved in this study. Individuals are genotyped by TNFR1 gene promoter sequencing, and TNFR1 serum levels were measured by the ELISA quantitative method. Concerning TNFR1 -609 G/T locus, we noticed that the T allele was associated with an attenuated susceptibility to GC (OR = 0.4; p value = 0.02). At the genotypic level and under the recessive model, the TNFR1 -609 TT genotype showed a decreased risk of GC (OR = 0.3, p value = 0.03) compared to the combined (GG/GT) genotypes. TNFR1 serum levels have been increased together with gastric lesion severity (p value < 0.05). The TNFR1 -609 TT genotype seemed linked to a low level of sTNFR1 compared to GT and GG genotypes (p value = 0.07). Concerning TNFR1 -580 A/G locus, no significant relation was noticed between this polymorphism and GC susceptibility, as well as with the TNFR1 serum level. Our results suggest that the TNFR1 -609 T allele appears to have a protective effect against GC. High levels of TNFR1 serum levels seemed to be associated with the aggressiveness of gastric lesions. Therefore, our results suggest that TNFR1 -609 T/G polymorphism and the TNFR1 serum levels may be related to GC susceptibility.

Association of MMP-9 polymorphisms with diabetic nephropathy risk: A protocol for systematic review and meta-analysis.

Background:Diabetic nephropathy (DN) is a multifactorial disease with gene–environment interaction resulting in progressive renal function damage. Multiple studies have assessed the association between matrix metalloproteinase-9 (MMP-9) gene promoter polymorphism and DN susceptibility. However, the results are inconclusive. In the present study, we will conduct a meta-analysis to further examine this relationship more precisely.Methods:Electronic databases (Pubmed, Web of Science, Embase, Google Scholar, Wanfang, China Biological Medicine and China National Knowledge Infrastructure) will be used to search clinical case–control studies about MMP-9 polymorphism and DN published until 18 August 2020. The language will be restricted to Chinese and English. Two reviewers will take charge of completing the selection of study, the extraction of data as well as the assessment of study quality independently. The Newcastle-Ottawa Scale will be used to evaluate the study quality. We will evaluate the association under 5 genetic models. Fixed-effects or random-effects models will be used to calculate the effect sizes of odds ratio and 95% confidence intervals. Afterwards, subgroup analysis will be conducted in terms of the ethnicity and genotyping method. Additionally, sensitivity analysis will be performed via sequentially omitting each of the included studies one at a time. The funnel plots, Egger regression test, and Begg rank correlation test will be used to test the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0.Results:This protocol reported according to the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. This study will provide a better understanding of the association between MMP-9 polymorphisms and DN risk.Conclusion:Publishing this protocol will minimize the potential bias related to data mining, thus contributing to generation of reliable evidence.OSF registration number:DOI 10.17605/OSF.IO/H5FS4

The Influence of −174 G/C Interleukin 6 Promoter Gene Polymorphism to Interleukin 6 Concentration in the End Stage Renal Disease Patients with Dialysis: A Single-center Experience in Indonesia

BACKGROUND: Chronic kidney disease (CKD) is classified as a multifactorial disease as a combination of genetic and environmental factors that affect the onset and progression of end-stage renal disease (ESRD). In the last decades are recognized that inflammation, where the critical modulator is cytokines, can occur before the onset of kidney disease and can be a causative factor in the development of CKD. Interleukin (IL)-6 has several polymorphisms in the promoter region, such as 174 G-C, 634 C-G, 572 G-C, and 597 G-A. G/C single nucleotide polymorphism of the IL-6 gene at position 174 in the promoter region is reported to affect the level of IL-6 expression. Unfortunately, there is a lack of data about the genotype frequencies of -174 G/C IL-6 promoter gene polymorphism in Indonesian with ESRD.&#x0D; AIM: This study aimed to analyze whether −174 G/C IL-6 promoter gene polymorphism influences the concentration of IL-6 in ESRD patients with dialysis in Indonesia.&#x0D; METHODS: We recruited 95 outpatients who were undergoing regular hemodialysis for ≥3 months at the Rasyida Renal Hospital, Medan, in this cross-sectional study. IL-6 genotype polymorphism was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay method was performed to assess the quantitative IL-6 serum.&#x0D; RESULTS: PCR-RFLP examination showed the frequency distribution of the IL-6 genotype -174 G/C gene; 72 (75.8%) respondents had GG genotypes; 22.1% of respondents had the CG genotype, and (2.1%) had the CC genotypes. Patients with the CC genotype were statistically significant to have higher IL-6 concentration compared to other genotypes (p &lt; 0.001). Likewise, with diabetic patients, statistics showed higher IL-6 concentration compared to non-diabetics patients (p &lt; 0.001).&#x0D; CONCLUSION: This is the first study showing that -174 G/C IL-6 promoter gene polymorphism influences the IL-6 concentrations in ESRD patients with dialysis in Indonesia. Multicenter studies are needed to validate these findings.

Association Analysis of Monoamine Oxidase-A Gene Promoter Polymorphism (MAOA uVNTR) for Antisocial Behavior: Absence of the Counting Number Repeats in Central Iran

Background: The MAOA gene is located on the X chromosome (Xp11.23). Several studies have established a VNTR (Variable Number Tandem Repeat) polymorphism in the upstream of the MAOA gene transcriptional initiation region named uVNTR which is correlated with the risk of antisocial behavior. Objectives: This study aimed to investigate the association between MAOA genotypes and the risk of violent behavior in a cohort of violent and age-matched non-violent individuals. Methods: In the current case-control study, MAOA uVNTR was genotyped in a cohort of 88 violent and 95 age-matched non-violent individuals. Individuals were genotyped for the MAOA uVNTR by performing PCR, gel electrophoresis, and sequencing. Furthermore, a chi-square test was performed using SPSS, and a p-value of less than 0.05 was considered statistically significant. Results: We identified three MAOA uVNTR allelic variants: They were harboring 3.5, 4.5, and 5.5 repeated sequences. Alleles with 2, 3, 4, 5, and 6 repeats were not observed in any of the two examined groups. Conclusions: We did not detect a statistically appreciable association between antisocial behavior and allele frequencies in the studied population in central Iran.

The serotonin transporter gene polymorphism (SLC6A4) and risk for psychiatric morbidity and comorbidity in the Baltimore ECA follow-up study

BackgroundThe human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sample. Methods628 participants, mean age 48.3 years old, were assessed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. Associations between 5HTTLPR and the prevalence, comorbidity, and time-to-diagnoses for 16 psychiatric conditions were evaluated, using several analytical approaches. ResultsThe SERT S allele was significantly associated with an increased lifetime prevalence of panic disorder. There was a “protective” association between SERT gene S allele carrier status and the risk of obsessive-compulsive disorder (OCD) in time-to-event analysis. Carriers of the S allele had a significant increased risk of two specific comorbid disorder pairs: major depressive disorder (MDD) and social phobia, and MDD and agoraphobia. Overall, there was no increased risk of receiving an initial or an additional diagnosis for a mental disorder in the SERT S allele carriers ConclusionsThe findings suggest that the S allele carrier status is associated with an increased prevalence of panic disorder in a community sample. There was an increased risk for comorbidity in a more homogeneous subgroup of cases with MDD and social phobia, as well as or agoraphobia. Our findings suggest a specific effect of the SERT promoter gene polymorphism on a subgroup of individuals identifiable by their comorbidity.

Study the Association of Tumor Necrosis Factor Promoter Polymorphism with Type 2 Diabetic Nephropathy.

Type 2 Diabetes Mellitus (T2DM) is well known to include an inflammatory component that has been considered to be related to diabetic complications. Diabetic nephropathy (DN) is one of the significant complications as it constitutes the most frequent cause of end-stage renal disease. Tumor Necrosis Factor-α (TNF-α) is known as a multifunctional proinflammatory cytokine which is associated with some pathological processes such as immunoregulation, proliferation, inflammation, and apoptosis. The aim was to explore the association between the TNF-α promoter -1031T/C single nucleotide polymorphism (SNP) and the serum TNF-α level in addition to nephropathy among type 2 diabetic patients. The study included 38 T2DM subjects without nephropathy (DM group), 40 subjects with DN, and 20 controls. Identification of TNF-α promoter gene polymorphism -1031T/C was done by PCR-RFLP, and genotyping was confirmed by direct sequencing. The serum TNF-α level was assessed by ELISA. Correlations were tested by Pearson's correlation analysis. Logistic regression was used to detect the most independent factor for development of DN. The serum level of TNF-α in the DM group was significantly higher than controls (p < 0.001); also, the DN group was considerably higher than controls and DM without nephropathy (p < 0.001). Also, there was a significant positive correlation between serum levels of TNF-α with FBG (fasting blood glucose), creatinine, total cholesterol, LDL-C, HbA1c, and microalbumin/creatinine ratio (ACR) among the DN group (p = 0.042, <0.001, <0.001, <0.001, 0.027, and 0.043, respectively). Mutant homozygous CC and heterozygous TC genotypes were higher in DN than in DM and controls. C allele was more represented in DN than in DM and controls (p = 0.003) while T allele was higher in controls than in DM and DN patients. The levels of TNF-α were higher in subjects who had mutant CC than the wild TT genotype among DN (p < 0.001). C allele was more risky for DN than T allele between DN and controls by 5.4-fold (CI: 1.75-16.68) as well as between DN and DM by 2.25-fold (CI: 1.1-4.59). Conclusion. Serum levels of TNF-α were higher in individuals with mutant CC genotype of -1031T/C TNF-α gene, and C allele could be associated with increased risk for nephropathy among patients with T2DM.

Association of the -629C>A (rs1800775) CETP Polymorphism with the Development of Essential Hypertension in Mexican Population.

Introduction: Polymorphisms in the CETP gene promoter have been associated with cardiovascular risk and lipid alterations; however, their role in the development of hypertension has not been extensively explored. We evaluated four polymorphisms of the CEPT gene -827C>T, -631C>A, -630C>A, and -629C>A in patients with essential hypertension (EH). Materials and Methods: A total of 160 hypertensive (HT) patients and 160 normotensive (NT) individuals were studied. Blood pressure was measured and blood samples were collected for biochemical anlayses and DNA extraction. Polymorphisms were identified using Sanger sequencing. Genotype, genotype combination, allele, and haplotype frequencies were analyzed. Associations between the SNPs and EH were explored using multiple linear regression models. Results: Under the dominant model, the -629A allele reduced the odds of having EH (odds ratio [OR] = 0.58, 95% confidence interval [CI], 0.34-0.98; p = 0.04), whereas the genotype combination -631CC/-629CC increased the risk of HT (OR = 2.21, 95% CI, 1.23-3.95, p = 0.008). In HT patients, the -629A allele was associated with increased insulin levels (β = 4.0, 95% CI, 1.21-6.68, p = 0.005), and homeostatic model assessment of insulin resistance (β = 0.9, 95% CI, 0.17-1.72, p = 0.018), and in NT individuals it was associated with increased high-density lipoprotein cholesterol levels (β = 3.0, 95% CI, 0.20-5.78, p = 0.036). Conclusion: The CETP -629A allele reduces the odds of having essential arterial hypertension in the Mexican population. Moreover, it exerts a variable effect on diverse biomarkers analyzed in both NT and HT groups.

2150-PUB: Chemotactic Cytokine Receptor 5 (CCR5) Gene Promoter Polymorphism (rs1799987) Is Associated with the Risk of Diabetic Kidney Disease in Polish Patients with Type 2 Diabetes

Background and Aims: The environmental risk factors of diabetic kidney disease (DKD) do not allow identification of people at higher risk of it. A lot of expectations are being placed to the genetic predisposition. Among patients with diabetes, the presence of CCR5 gene polymorphism is suspected to be associated with DKD, yet the results are inconclusive. The aim of this study was to evaluate its association with DKD among Polish patients with type 2 (T2DM). Materials and Methods: CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among 467 consecutive patients with T2DM visiting one outpatient diabetology clinic in Upper Silesia, Poland. DKD diagnosis was based on urinary albumin creatinine ratio &amp;gt;300 mg/g and the presence of diabetic retinopathy. Information related to time of diabetes duration and HbA1c were collected. Results: Clinical characteristic of studied patients is presented in Table 1. We found that both GG genotype (p=0.035) and allele G (p=0.02) were significantly associated with DKD occurrence and G allele was present in all of the DKD patients. Conclusion: A significant association between rs1799987 polymorphism of CCR5 gene and the presence of DKD in the group of Polish patients with T2DM was found what is in accordance with some previous studies. Further studies are needed in this area to confirm this association. Disclosure K. Nabrdalik: None. P.S. Pokrzywnicka: None. H. Kwiendacz: None. P. Adamczyk: None. D. Moczulski: None. H. Moczulska: None. K. Drozdz: None. W. Grzeszczak: None. J. Gumprecht: Consultant; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier. Speaker’s Bureau; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier.

CORRELATION BETWEEN POLYMORPHISMS OF FOXP3 T-REGULATORY PROMOTOR GENE WITH TGF-β IN PATIENTS WITH GRAVES’ DISEASE

Objective: The aim of this study is to prove that there are Forkhead Box P3 (FOXP3) T-regulator promoter polymorphisms in Graves’ disease and to analyze the association between FOXP3 T-regulator promoter polymorphisms with transforming growth factor (TGF)-β levels.&#x0D; Methods: This study was an observational study with cross-sectional comparative study design. Consecutive sampling was conducted in patients with Graves’ disease who came to the outpatient clinic and treated in Dr. M. Djamil Hospital, Padang. Blood sampling was performed on 30 Graves’ subjects and 30 control subjects based on inclusion and exclusion criteria. DNA isolation, primary construction, and polymorphism identification by polymerase chain reaction method and blood sample examination by enzyme-linked immunosorbent assay techniques method for TGF-β examination were performed in this study.&#x0D; Results: The results of this study obtained the most age of patients with Graves’ disease is 30–40 years with the female gender. Graves’ patient group was found to have 86.7% of single nucleotide polymorphisms (SNP) rs3761548 polymorphism, and 61.3% had SNP rs2232365 polymorphism followed by 26.7% polymorphism of SNP rs3761547 and rs3761549, and no SNP rs2232364 polymorphism was found. In Graves’ group, the mean value of TGF-β was 1030.01±277.64 ng/ml, significantly higher than the control group. Statistical analysis showed a significant relationship between polymorphism of the FOXP3 promoter gene and TGF-β level with p&lt;0.05.&#x0D; Conclusion: This study proves that there are polymorphisms of the FOXP3 promoter gene in Graves’ patients, especially SNP rs3761548 and rs2232365. The polymorphism of the FOXP3 promoter gene has a significant association with TGF-β levels.

Association between VEGF gene promoter polymorphisms and bladder cancer: An updated meta-analysis

BackgroundVascular endothelial growth factor (VEGF) is the key regulator of angiogenesis in the development of various cancers. Previous studies have examined the relationship between VEGF gene promoter polymorphisms such as −2578C/A and −460C/T and bladder cancer risk; however, these results are inconclusive. Therefore, we performed this meta-analysis to investigate the association between VEGF gene promoter polymorphisms and bladder cancer risk. MethodsPubMed, Embase, Cochrane Library and Web of Science databases were searched for studies published before September 2018. The methodological quality assessment of included studies was performed based on the Newcastle-Ottawa Quality Scale (NOS). We conducted a systematic review and meta-analysis using both fixed- and random-effect model. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the relationship. In addition, the stability of our analysis was evaluated by heterogeneity, sensitivity, subgroup of ethnicity, and publication bias analysis. ResultsWe finally included 7 case-control studies with a total of 2412 bladder cancer patients and 3157 cancer-free controls. In Asian population with the VEGF −2578C/A polymorphism, significantly higher bladder cancer risks of 1.55 (95% CI = 1.25–1.93) and 1.53 (95% CI = 1.11–2.10) were found in the heterozygous model (AC vs CC) and the dominant model (AA + AC vs CC), respectively. Though there was no statistical association between VEGF −460C/T polymorphism and bladder cancer, a tendency to higher bladder cancer risk was observed in various genetic models (T vs C; TT vs CC; TC vs CC and TT + TC vs CC). ConclusionsOur findings suggest that VEGF −2578C/A polymorphism might be a risk factor with a modest significance for bladder cancer only in Asian population. Further studies with a larger sample size and other functional polymorphisms are needed to explore the effects of VEGF gene on the risk of bladder cancer.