Bp Variable Number Of Tandem Repeats Research Articles

TRIB3 promoter 33bp VNTR is associated with the risk of cerebrovascular disease in type 2 diabetic patients.

Previous studies have demonstrated that TRIB3 is closely related to insulin resistance, metabolic disorders and vascular diseases. Recently, it was reported that a 33 bp variable number of tandem repeats (VNTR) located in the TRIB3 promoter could considerably alter its transcriptional activity. Nonetheless, whether the shift of TRIB3 transcriptional activity has the effect of inducing diabetic vascular complications is still unclear. Therefore, in our study, we aimed to explore the relationship between the TRIB3 33bp VNTR and diabetic vascular complications. The TRIB3 33bp VNTR polymorphisms were determined by PCR and Sanger sequencing, a total of 798 eligible Chinese patients with type 2 diabetes (T2DM) were included in our study and then evaluated with clinical data. After adjusting for age, gender, BMI, smoking history, drinking history and duration of diabetes, we found that the high number of 33 bp tandem repeats (repeats>8) was significantly associated with an increase in the risk of cerebrovascular diseases compared with the low number of 33 bp tandem repeats (repeats≤6) in patients with T2DM(OR 2.66, 95% CI 1.29–5.47, p = 0.008). The intermediate number of 33bp tandem repeats (6 < repeat≤8) was markedly associated with a decreased risk of diabetic retinopathy compared with the low number of tandem repeats (OR 0.65, 95% CI 0.46–0.91, p = 0.012). Adjusting for gender, age and BMI, there was a significant difference in DBP levels among patients with the number of different 33 bp tandem repeats (Low vs. Intermediate vs. High, 81.6 ± 12.8 vs. 79.8 ± 12.4 vs. 78.7 ± 12.6 mmHg; p = 0.045). Subgroup analysis found that TRIB3 VNTR was significantly correlated with the difference in systolic blood pressure (SBP) in T2DM patients taking ACEI/ARB drugs (Low vs. Intermediate vs. High, 146.27 ± 18.23 vs. 140.01 ± 19.91 vs. 140.77 ± 18.64 mmHg; p = 0.018). Our results indicated that TRIB3 promoter 33bp VNTR is related to vascular diseases in T2DM patients, and may serve as a new biomarker for individualized prevention and therapy of T2DM.

Congenital idiopathic megaesophagus in the German shepherd dog is a sex-differentiated trait and is associated with an intronic variable number tandem repeat in Melanin-Concentrating Hormone Receptor 2.

Congenital idiopathic megaesophagus (CIM) is a gastrointestinal (GI) motility disorder of dogs in which reduced peristaltic activity and dilation of the esophagus prevent the normal transport of food into the stomach. Affected puppies regurgitate meals and water, fail to thrive, and experience complications such as aspiration pneumonia that may necessitate euthanasia. The German shepherd dog (GSD) has the highest disease incidence, indicative of a genetic predisposition. Here, we discover that male GSDs are twice as likely to be affected as females and show that the sex bias is independent of body size. We propose that female endogenous factors (e.g., estrogen) are protective via their role in promoting relaxation of the sphincter between the esophagus and stomach, facilitating food passage. A genome-wide association study for CIM revealed an association on canine chromosome 12 (P-val = 3.12x10-13), with the lead SNPs located upstream or within Melanin-Concentrating Hormone Receptor 2 (MCHR2), a compelling positional candidate gene having a role in appetite, weight, and GI motility. Within the first intron of MCHR2, we identified a 33 bp variable number tandem repeat (VNTR) containing a consensus binding sequence for the T-box family of transcription factors. Across dogs and wolves, the major allele includes two copies of the repeat, whereas the predominant alleles in GSDs have one or three copies. The single-copy allele is strongly associated with CIM (P-val = 1.32x10-17), with homozygosity for this allele posing the most significant risk. Our findings suggest that the number of T-box protein binding motifs may correlate with MCHR2 expression and that an imbalance of melanin-concentrating hormone plays a role in CIM. We describe herein the first genetic factors identified in CIM: sex and a major locus on chromosome 12, which together predict disease state in the GSD with greater than 75% accuracy.

Childhood trauma and genetic variation in the DAT 40-bp VNTR contribute to HIV-associated neurocognitive disorders.

HIV/AIDS is a major public health burden in South Africa, currently affecting an estimated 13.5% of the population. Despite improved access to antiretroviral therapies, HIV-associated neurocognitive disorders (HAND), characterised by a spectrum of neurocognitive impairment, emotional disturbances and motor abnormalities, continue to persist. Gene-environment interactions contribute to HAND pathophysiology and previous research has identified childhood trauma as an environmental risk factor. Dopaminergic signalling in the prefrontal cortex plays a key role in cognitive function. Thus, variants in genes encoding the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT), which are responsible for dopamine transport and metabolism, could represent genetic risk factors for HAND. This study investigated whether the DAT variable number of tandem repeats (VNTR) and COMT Val158Met (rs4680) polymorphisms are associated with longitudinal change in cognitive function in the context of childhood trauma and HIV. Participants (n = 49 HIV-negative and n = 64 HIV-positive women) completed the Childhood Trauma Questionnaire – Short Form (CTQ-SF) and provided blood for genetic analyses. Global cognitive scores were generated from baseline and one-year follow-up assessments. Following polymerase chain reaction, genotypes were determined using gel electrophoresis and confirmed by Sanger sequencing. Baseline global cognitive scores, genotype, HIV status and CTQ-SF scores were regressed on one-year global cognitive scores in regression models. Analysis of variance was used to examine the effect of including predictor variable interactions on model fit. HIV seropositivity was associated with poorer cognitive performance at one-year follow-up (p = 2.46 ×10−4). The combination of HIV and DAT 10-repeat homozygosity (DAT 10/10) was associated with reduced global cognitive scores in longitudinal models (p = 0.010). Including the interaction between DAT 10/10, childhood trauma, and HIV explained significantly more of the variance in longitudinal cognitive scores (p = 0.008). There were no significant associations with the COMT genotype. Our research indicates that childhood trauma and genetic variation in DAT contribute toward the aetiology of HAND. Future studies in larger cohorts are warranted to verify these results.

The Association between a MAOB Variable Number Tandem Repeat Polymorphism and Cocaine and Opiate Addictions in Polyconsumers.

Genetic analysis of the association between alcohol, cocaine, and opiate addiction and variable number tandem repeat (VNTR) polymorphisms in monoamine oxidase B (MAOB) and serotonergic 5-hydroxytryptamine (serotonin) receptor 1B and 2C (HTR1B 21 and HTR2C) pathway genes was performed in a sample of 302 polyconsumers. Our genetic association analysis revealed a significant association between a 184 base pair (bp) VNTR polymorphism in the MAOB gene and addiction to cocaine and opiates. This work highlights new genetic marker associations in cocaine and opiate polyconsumer addictions. These data help to clarify and quantify the complex role of genetics in addictive disorders, as well as their future contribution to the prevention (genetic counselling), diagnosis (genetic diagnosis of vulnerability), and treatment (pharmacogenomics) of these disorders.

Association analyses reveal gender-specific associations of DAT140-bp VNTRand -839C/T polymorphisms with obsessive-compulsive disorder and obsessive-compulsive symptoms.

The dopamine transporter (DAT) is involved in dopamine signaling and distribution, controlling dopamine concentrations and contributing to several central nervous system disorders. The purpose of this study was to determine the association between two functional polymorphisms in DAT1 gene, the 40-base pair Variable Number of Tandem Repeats (VNTR) and the Single Nucleotide Polymorphism (SNP) -839C/T and obsessive-compulsive disorder (OCD) and/or its clinical features. To do so, 199 OCD patients and 201 healthy controls were genotyped using Polymerase Chain Reaction (PCR). Genotype distribution of both polymorphisms was in Hardy-Weinberg equilibrium. Although OCD and controls did not differ in terms of polymorphisms distribution, we observed that the presence of 10R-allele protected men of having OCD (P = 0.03). We also observed a significant association between the presence of 10R and checking in women (P = 0.02; OR = 3.14; 95%CI 1.08-9.11), and between the 9/9 genotype and neutralization in men (P = 0.04; OR = 3.38; 95%CI 1.03-11.11). Finally, the T-allele of -839C/T was significantly associated with the "obsession" score (P = 0.02; OR = 2.66; 95%CI 1.15-6.13). Our results demonstrate an important influence of dopaminergic pathways, particularly DAT1 polymorphisms, in OCD.

Association between IL-1RN VNTR polymorphism and head and neck cancer in Indonesian population

The interleukin-1 receptor antagonist (IL-1RN) is a natural antagonist of IL-1 receptors, and its 86-bp variable number tandem repeat (VNTR) polymorphism within intron 2 has been associated with the development of several cancers. This study aimed to evaluate the IL-1RN polymorphism for its potential association with head and neck cancer in Indonesia population. Polymerase chain reaction analysis was performed on stored blood-derived DNA samples from 110 control participants and 90 patients with head and neck cancer for the IL-1RN VNTR polymorphism. Chi-square and odds ratio were used for the statistical analysis. This study showed no significant difference in the frequencies of genotypes or alleles in either the control or the cancer groups. However, a larger sample size could reveal a more significant difference between the groups. The IL-1RN VNTR polymorphism was not associated with head and neck cancer in the studied Indonesian population.

Lack of association between interleukin-1 receptor antagonist gene 86-bp VNTR polymorphism and ischemic stroke: A meta-analysis.

The results of published studies which examined the association between variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1RN) and ischemic stroke (IS) are conflicting. Thus, we performed a meta-analysis to examine the potential association between IL-1RN VNTR polymorphism and IS risk. A systematic literature search of PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, CQVIP, and WANFANG Database identified 10 studies with 2331 cases and 3335 controls. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to evaluate the strength of the association. Subgroup analysis and meta-regression analysis were used to investigate the potential sources of heterogeneity. Begg funnel plots were used to explore the publication bias. In this study, no enough proof was found to prove the association between IL-1RN 86-bp VNTR polymorphism and IS risk with random-effects model in the homozygous model (1/1 vs 2/2, OR = 0.97, 95% CI = 0.50-1.87, Pheterogeneity = .00), the heterozygous model (1/2 vs 2/2, OR = 0.64, 95% CI = 0.41-1.01, Pheterogeneity = .10), the dominant model (1/1 + 1/2 vs 2/2, OR = 0.85, 95% CI = 0.51-1.42, Pheterogeneity = .02), the recessive model (1/1 vs 1/2 + 2/2, OR = 0.69, 95% CI = 0.46-1.03, Pheterogeneity = .00), and allelic model (1 vs 2, OR = 1.24, 95% CI = 0.89-1.74, Pheterogeneity = .00). A marginally significant negative association was observed between IL-1RN 86-bp VNTR polymorphism and IS risk in the heterozygous model in the fixed-effects model (1/2 vs 2/2, OR = 0.71, 95% CI = 0.53-0.95, Pheterogeneity = .10). In subgroup analyses, similar association was found in the group whose control size was lower than 300. In conclusion, our results suggested that there was no sufficient evidence to support the association between IL-1RN 86-bp VNTR polymorphism and IS. Further large epidemiologic studies need to be done to confirm these findings.

Investigation of the role of interleukin-1 receptor antagonist VNTR variant on the Behçet's disease.

Behçet's disease (BD), a chronic multisystem inflammatory disorder, is mainly characterized by relapsing periods of a wide range of clinical symptoms. Several cytokine genes may play important roles in the pathogenesis of BD. Therefore, interleukin-1 receptor antagonist (IL-1Ra) gene 86bp variable number tandem repeat (VNTR) variant was investigated in patients with BD in a Turkish population. One hundred nine patients (60 females, 49 males; the mean age±standard deviation [SD] was 36.56±9.571 years) with BD and one hundred healthy individuals (54 females, 46 males; the mean age±SD was 36.64±2.294 years) were examined in the study. For genotyping, polymerase chain reaction-restriction fragment length polymorphism analysis was employed. Data were analyzed using Statistical Package for Social Sciences (SPSS) 22.0 (IBM Corp.; Armonk, NY, USA) (p<0.05). The genotype distribution and allele frequencies of the IL-1Ra VNTR variant did not differ significantly between the patients and the controls (p>0.05). The frequency of the a1/a1, a1/a2 genotypes and a1, a2 alleles were the most common both in patients and healthy controls (p=0.37, p=0.26, and p=0.53, respectively). Also, no statistically significant difference was found between the IL-1Ra VNTR variant genotypes and clinical characteristics (p>0.05). The results of this study do not support an association between the IL-1Ra VNTR variant and the risk of BD in a Turkish population. However, further studies of this variant with larger sample sizes and different ethnicities are required for confirmation.

The Allele 2 of the VNTR Polymorphism in the Gene That Encodes a Natural Inhibitor of IL-1β, IL-1RA Is Favorably Associated With Chronic Otitis Media.

Objectives Chronic otitis media (COM) is followed by irreversible tissue damage and destruction of the middle ear structures, with the possibility of complications under the maintenance of inflammation. Inflammatory mediators such as cytokines play a crucial role in the initial stage of inflammation. The aim of this study was to evaluate the association of the polymorphisms in two innate immunity/inflammation cascade genes from interleukin-1 (IL-1) gene cluster with COM with regard to cholesteatoma.Methods In the cross-sectional case-control study, DNA samples were collected from 189 patients with COM and 119 controls from a population of Serbia. The +3953 C/T (rs1143634), TaqI polymorphism in interleukin-1 beta (IL-1β) gene and 86 bp variable number tandem repeat (VNTR, rs2234663) polymorphism in the IL-1 receptor antagonist (IL-1RA) gene were analyzed by polymerase chain reaction.Results The IL-1β TaqI polymorphism was not significantly different in patients compared with the control group. The significant difference between patients and controls was observed for both, genotype and allele frequencies of IL-1RA VNTR polymorphism (chi-square P<0.01). We found that carriers of IL-1RA allele 2 (odds ratio, 0.47; 95% confidence interval, 0.29 to 0.76; P=0.004) have a favorable association with COM, using multivariate logistic analysis that included both polymorphisms, age and sex. The IL-1RA allele frequency distribution was significantly different with regard to cholesteatoma.Conclusion The carriers of allele 2 of VNTR IL-1RA polymorphism had a decreased odds ratio for COM, which is in agreement with findings in other inflammatory disease and its previous association with higher IL-1RA levels. Possible down-regulation of IL-1 mediated proinflammatory signaling pathways via IL-1RA in COM as well as results of our study should be further investigated and replicated.

A meta-analysis of data associating DRD4 gene polymorphisms with schizophrenia.

To explore the association between DRD4 polymorphisms and schizophrenia risk, a meta-analysis was carried out with 41 case–control articles. Specifically, we included 28 articles (5,735 cases and 5,278 controls) that pertained to the 48 bp variable number tandem repeat (VNTR) polymorphism, nine articles (1,517 cases and 1,746 controls) that corresponded to the 12 bp tandem repeat (TR), six articles (1,912 cases and 1,836 controls) that addressed the 120 bp TR, 10 articles (2,927 cases and 2,938 controls) that entailed the −521 C>T polymorphism, six articles (1,735 cases and 1,724 controls) that pertained to the −616 C>G polymorphism, and four articles (1,191 cases and 1,215 controls) that involved the −376 C>T polymorphism. Pooled analysis, subgroup analysis, and sensitivity analysis were performed, and the data were visualized by means of forest and funnel plots. Results of pooled analysis indicated that the −521 CC variant (Pz=0.009, odds ratio [OR] =1.218, 95% confidence interval [CI] =1.050–1.413) and genotype L/L (ie, long allele) of the 120 bp TR were risk factors of schizophrenia (Pz=0.004, OR =1.275, 95% CI =1.081–1.504). The 48 bp VNTR, the 12 bp TR, the −616 C>G polymorphism, and the −376 C>T polymorphism were not associated with schizophrenia. Additional research is warranted to explore the association between polymorphisms of DRD4 and schizophrenia risk.

Evaluation of VNTR polymorphisms of dopamine transporter gene and the risk of bipolar disorder in Zahedan, southeast Iran.

The exact role of dopamine transporter gene (DAT1) in the pathogenesis of bipolar disorder type 1 (BD) is not understood. In the present study, we aimed to evaluate the possible association between 30, 40 and 63 bp variable number tandem repeat (VNTR) polymorphisms of DAT1 gene and the risk of type 1 (BD) in a sample of Iranian population. This case-control study was performed on 152 BD patients and 153 psychiatrically healthy subjects. Genotyping of the variant was done by polymerase chain reaction method. Totally, the findings did not support an association between DAT1 VNTR polymorphisms and the risk of BD in a sample of southeast Iranian population.

Genetically-Driven Enhancement of Dopaminergic Transmission Affects Moral Acceptability in Females but Not in Males: A Pilot Study.

Moral behavior has been a key topic of debate for philosophy and psychology for a long time. In recent years, thanks to the development of novel methodologies in cognitive sciences, the question of how we make moral choices has expanded to the study of neurobiological correlates that subtend the mental processes involved in moral behavior. For instance, in vivo brain imaging studies have shown that distinct patterns of brain neural activity, associated with emotional response and cognitive processes, are involved in moral judgment. Moreover, while it is well-known that responses to the same moral dilemmas differ across individuals, to what extent this variability may be rooted in genetics still remains to be understood. As dopamine is a key modulator of neural processes underlying executive functions, we questioned whether genetic polymorphisms associated with decision-making and dopaminergic neurotransmission modulation would contribute to the observed variability in moral judgment. To this aim, we genotyped five genetic variants of the dopaminergic pathway [rs1800955 in the dopamine receptor D4 (DRD4) gene, DRD4 48 bp variable number of tandem repeat (VNTR), solute carrier family 6 member 3 (SLC6A3) 40 bp VNTR, rs4680 in the catechol-O-methyl transferase (COMT) gene, and rs1800497 in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene] in 200 subjects, who were requested to answer 56 moral dilemmas. As these variants are all located in genes belonging to the dopaminergic pathway, they were combined in multilocus genetic profiles for the association analysis. While no individual variant showed any significant effects on moral dilemma responses, the multilocus genetic profile analysis revealed a significant gender-specific influence on human moral acceptability. Specifically, those genotype combinations that improve dopaminergic signaling selectively increased moral acceptability in females, by making their responses to moral dilemmas more similar to those provided by males. As females usually give more emotionally-based answers and engage the “emotional brain” more than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process.

The significance of IL-1β +3953C>T, IL-6 -174G>C and -596G>A, TNF-α -308G>A gene polymorphisms and 86 bp variable number tandem repeat polymorphism of IL-1RN in bronchopulmonary dysplasia in infants born before 32 weeks of gestation.

IntroductionBronchopulmonary dysplasia (BPD) is a chronic lung disease that affects primarily preterm infants. Genetic factors are also taken into consideration in the pathogenesis of BPD. Genetic predispositions to higher production of inflammation mediators seem to be crucial. Material and methodsThe aim of this study was to evaluate the possible relationship between polymorphisms: interleukin-1β +3953 C>T, interleukin-6 -174 G>C and -596 G>A, tumour necrosis factor -308 G>A and interleukin-1RN VNTR 86bp and the occurrence of BPD in a population of 100 preterm infants born from singleton pregnancy, before 32+0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. ResultsIn the study population BPD was diagnosed in 36 (36%) newborns. Among the studied polymorphisms we found the higher prevalence for BPD developing of the following genotypes: 1/2 (OR 1.842 [0.673-5.025] and 2/2 IL-1RN (OR 1.75 [0.418-6.908] 86bpVNTR; GC (2.222 [0.658-8.706]) and CC IL-6 -174G>C (1.6 [0.315-8.314]) and GA (2.753 [0.828-10.64]) and AA (1.5 [0.275-8.067] IL-6 -596G>A), GA 1.509 (0.515-4.301) TNF-α -308G>A. However, these finding were not statistically significant.ConclusionsGenetic factors are undeniably involved in the pathogenesis of BPD. In the times of individualised therapy finding genes responsible for BPD might allow the development of new treatment strategies. A new way of specific therapy could ensure the reduction of complications connected with BPD and treatment costs.

Self-Reported Sexual Behavioral Interests and Polymorphisms in the Dopamine Receptor D4 (DRD4) Exon III VNTR in Heterosexual Young Adults.

Polymorphisms in the dopamine D4 receptor (DRD4) have previously been shown to associate with a variety of human behavioral phenotypes, including ADHD pathology, alcohol and tobacco craving, financial risk-taking in males, and broader personality traits such as novelty seeking. Recent research has linked the presence of a 7-repeat (7R) allele in a 48-bp variable number of tandem repeats (VNTR) along exon III of DRD4 to age at first sexual intercourse, sexual desire, arousal and function, and infidelity and promiscuity. We hypothesized that carriers of longer DRD4 alleles may report interest in a wider variety of sexual behaviors and experiences than noncarriers. Participants completed a 37-item questionnaire measuring sexual interests as well as Cloninger's Temperament and Character Inventory, and were genotyped for the 48-bp VNTR on exon III of DRD4. Based on our final genotyped sample of female (n=139) and male (n=115) participants, we found that 7R carriers reported interest in a wider variety of sexual behaviors (r=0.16) within a young adult heterosexual sample of European descent. To our knowledge, this is the first reported association between DRD4 exon III VNTR genotype and interest in a variety of sexual behaviors. We discuss these findings within the context of DRD4 research and broader trends in human evolutionary history.

DRD2 and DRD4 genes related to cognitive deficits in HIV-infected adults who abuse alcohol.

BackgroundHIV-infected individuals continue to experience neurocognitive deterioration despite virologically successful treatments. The causes of neurocognitive impairment are still unclear. However, several factors have been suggested including the role of genetics. There is evidence suggesting that neurocognitive impairment is heritable and individual differences in cognition are strongly driven by genetic variations. The contribution of genetic variants affecting the metabolism and activity of dopamine may influence these individual differences.MethodsThe present study explored the relationship between two candidate genes (DRD4 and DRD2) and neurocognitive performance in HIV-infected adults. A total of 267 HIV-infected adults were genotyped for polymorphisms, DRD4 48 bp-variable number tandem repeat (VNTR), DRD2 rs6277 and ANKK1 rs1800497. The Short Category (SCT), Color Trail (CTT) and Rey-Osterrieth Complex Figure Tests (ROCT) were used to measure executive function and memory.ResultsResults showed significant associations with the SNP rs6277 and impaired executive function (odds ratio = 3.3, 95 % CI 1.2–2.6; p = 0.004) and cognitive flexibility (odds ratio = 1.6, 95 % CI 2.0–5.7; p = 0.001). The results were further stratified by race and sex and significant results were seen in males (odds ratio = 3.5, 95 % CI 1.5–5.5; p = 0.008) and in African Americans (odds ratio = 3.1, 95 % CI 2.3–3.5; p = 0.01). Also, DRD4 VNTR 7-allele was significantly associated with executive dysfunction.ConclusionThe study shows that genetically determined differences in the SNP rs6277 DRD2 gene and DRD4 48 bp VNTR may be risk factors for deficits in executive function and cognitive flexibility.

Retraction Note to: Association of Catechol-O-methyltransferase val/met polymorphism with cognitive function in Gilles de la Tourette syndrome patients.

Gilles de la Tourette syndrome (GTS) is a kind of neuropsychiatric disorder with childhood onset. The cognitive dysfunction caused by GTS could affect the growth and learning of children and adolescents. The mechanism of cognitive functions was associated with dopaminergic system, thus we access the associations between polymorphism of some dopaminergic system-related genes including Catechol-O-methyltransferase (COMT) met/val, Dopamine receptor D4 (DRD4) exon III 48 bp VNTR (variable number of tandem repeats), Interleukin 1 (IL-1) Ra 86 bp and IL-1β exon 5, and cognitive functions in GTS patients. Genotyping analysis was performed through polymerase chain reaction (PCR). Test for cognitive functions of GTS patients included modified wisconsin card sorting test (WCST), trail making test, visual reproduction test, stroop test and verbal fluency test. The patients with COMT met/met genotype showed less perseverative errors in modified WCST test compared with patients with COMT val/val genotype (P < 0.05). Meanwhile, patients without allele val had better delayed memory in visual reproduction test, less errors in the stroop test and less perseverative errors in modified WCST test compared with patients with allele val (P < 0.05). However, no significant difference was found in cognitive functions among patients with different genotypes or alleles of polymorphisms of DRD4 exon III 48 bp VNTR, IL-1 Ra 86 bp and IL-1β exon 5 (P > 0.05). Polymorphism of COMT met/val was correlated with cognitive functions in GTS patients. This study provided basis for the analysis of molecular genetic pathology of cognitive dysfunctions in GTS.

A 40-bp VNTR polymorphism in the 3'-untranslated region of DAT1/SLC6A3 is associated with ADHD but not with alcoholism.

BackgroundADHD and alcoholism are psychiatric diseases with pathophysiology related to dopamine system. DAT1 belongs to the SLC6 family of transporters and is involved in the regulation of extracellular dopamine levels. A 40 bp variable number tandem repeat (VNTR) polymorphism in the 3′-untranslated region of DAT1/SLC6A3 gene was previously reported to be associated with various phenotypes involving disturbed regulation of dopaminergic neurotransmission.MethodsA total of 1312 subjects were included and genotyped for 40 bp VNTR polymorphism of DAT1/SLC6A3 gene in this study (441 alcoholics, 400 non-alcoholic controls, 218 ADHD children and 253 non ADHD children). Using miRBase software, we have performed a computer analysis of VNTR part of DAT1 gene for presence of miRNA binding sites.ResultsWe have found significant relationships between ADHD and the 40 bp VNTR polymorphisms of DAT1/SLC6A3 gene (P < 0.01). The 9/9 genotype appeared to reduce the risk of ADHD about 0.4-fold (p < 0.04). We also noted an occurrence of rare genotypes in ADHD (frequency different from controls at p < 0.01). No association between alcoholism and genotype frequencies of 40 bp VNTR polymorphism of DAT1/SLC6A3 gene has been detected.ConclusionsWe have found an association between 40 bp VNTR polymorphism of DAT1/SLC6A3 gene and ADHD in the Czech population; in a broad agreement with studies in other population samples. Furthermore, we detected rare genotypes 8/10, 7/10 and 10/11 present in ADHD boys only and identified miRNAs that should be looked at as potential novel targets in the research on ADHD.

Hardy-Weinberg equilibrium analysis of the 48 bp VNTR in the III exon of the DRD4 gene in a sample of parents of ADHD cases.

The aim of this study was to obtain the genotype and gene frequency from parents of children with attention-deficit/hyperactivity disorder (ADHD) and then assess the Hardy–Weinberg equilibrium of genotype frequency of the variable number tandem repeat (VNTR) III exon of the dopamine receptor D4 (DRD4) gene. The genotypes of the III exon of 48 bp VNTR repeats of the DRD4 gene were determined by polymerase chain reaction in a sample of 30 parents of ADHD cases. In the 60 chromosomes analyzed, the following frequencies of DRD4 gene polymorphisms were observed: six chromosomes (c) with two repeat alleles (r) (10%); 1c with 3r (1.5%); 36c with 4r (60%); 1c with 5r (1.5%); and 16c with 7r (27%). The genotypic distribution of the 30 parents was two parents (p) with 2r/2r (6.67%); 1p with 2r/4r (3.33%); 1p with 2r/5r (3.33%); 1p with 3r/4r (3.33%); 15p with 4r/4r (50%); 4p with 4r/7r (13.33); and 6p with 7r/7r (20%). A Hardy–Weinberg disequilibrium (χ2=13.03, P<0.01) was found due to an over-representation of the 7r/7r genotype. These results suggest that the 7r polymorphism of the DRD4 gene is associated with the ADHD condition in a Mexican population.

Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis.

We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B − 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of − 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B − 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD.

Association of Catechol-O-methyltransferase val/met polymorphism with cognitive function in Gilles de la Tourette syndrome patients.

Gilles de la Tourette syndrome (GTS) is a kind of neuropsychiatric disorder with childhood onset. The cognitive dysfunction caused by GTS could affect the growth and learning of children and adolescents. The mechanism of cognitive functions was associated with dopaminergic system, thus we access the associations between polymorphism of some dopaminergic system-related genes including Catechol-O-methyltransferase (COMT) met/val, Dopamine receptor D4 (DRD4) exon III 48 bp VNTR (variable number of tandem repeats), Interleukin 1 (IL-1) Ra 86 bp and IL-1β exon 5, and cognitive functions in GTS patients. Genotyping analysis was performed through polymerase chain reaction (PCR). Test for cognitive functions of GTS patients included modified wisconsin card sorting test (WCST), trail making test, visual reproduction test, stroop test and verbal fluency test. The patients with COMT met/met genotype showed less perseverative errors in modified WCST test compared with patients with COMT val/val genotype (P < 0.05). Meanwhile, patients without allele val had better delayed memory in visual reproduction test, less errors in the stroop test and less perseverative errors in modified WCST test compared with patients with allele val (P < 0.05). However, no significant difference was found in cognitive functions among patients with different genotypes or alleles of polymorphisms of DRD4 exon III 48 bp VNTR, IL-1 Ra 86 bp and IL-1β exon 5 (P > 0.05). Polymorphism of COMT met/val was correlated with cognitive functions in GTS patients. This study provided basis for the analysis of molecular genetic pathology of cognitive dysfunctions in GTS.