Bp VNTR Research Articles

Inflammatory and genomic interactions within keratoconus susceptible patients: a nationwide registered case–control study

PurposeThis study aimed to investigate the association between variants in the interleukin (IL)-1 gene cluster and susceptibility to keratoconus (KC) in an Iranian population.MethodsIn the case group, there were 188 KC patients diagnosed by clinical findings and corneal tomography. The control group included all 205 healthy controls with no personal or family history of eye-related, metabolic, or immune system-related disease. Using the standard salting out extraction procedure, genomic DNA was isolated from peripheral blood leukocytes. The genotypes were determined by applying agarose gel electrophoresis for the IL-1RN 86 bp VNTR and polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) for rs16944 and rs1143634.ResultsThe results showed a significant association between the IL-1β rs1143634 (rs1143634 T allele, P = 0.008) and IL-1RN 86 bp VNTR polymorphisms (LL and LS genotype, P = 0.048 and 0.012 respectively) and susceptibility to KC in the Iranian population. The genotype distributions of rs1143634 (P = 0.004) and rs2234663 (P = 0.042) significantly differed between case and control groups, with certain genotypes demonstrating a protective effect against KC. Logistic regression analysis revealed a protective effect of the IL-1RN L allele [odds ratio (OR) = 0.367, 95% confidence interval (CI): 0.240–0.562; P = 0.000] and certain haplotypes (OR = 0.628, 95% CI: 0.447–0.884; P = 0.007) against KC. However, no significant association was found for the IL-1β rs16944 polymorphism.ConclusionThis study provides evidence for an association between variants in the IL-1 gene cluster and susceptibility to KC in an Iranian population. Further research on larger and more diverse populations is warranted to validate these findings and explore the underlying mechanisms involved.

DRD4 VNTR 4/4 homozygosity as a genetic biomarker for treatment selection in patients with schizophrenia

ObjectiveThere seems to be an association between the DRD4 48-bp VNTR polymorphisms and antipsychotic treatment response, but there is a rare reference to confirm this finding. Hence, the present study tried to investigate the association between DRD4 48-bp VNTR polymorphisms and the treatment response of antipsychotics in patients with schizophrenia in Taiwan, using a propensity score matching (PSM) method. MethodsA total of 882 participants were enrolled in this study and completed informed consent, research questionnaires, including demographic information and the revised Chinese version Beliefs about Voices Questionnaire, and blood sampling. For descreasing of the selection bias and confounding variables, the PSM nearest neighbor matching method was used to select 765 paitents with schizophrenia (ratio of 1:8 between 85 persistent auditory hallucination and 680 controls) with matched and controlled the age and gender. ResultsSchizophrenia patients with DRD4 4 R homozygosity had a lower rate of good antipsychotic treatment response than the other DRD4 genotype carriers (DRD4 non-4/4). Among those 4 R homozygosity carriers, 60 cases of 503 (11.9%) retain persistent auditory hallucinations. Furthermore, this subgroup of patients is accounted for up to 70.6% of cases with poor neuroleptic treatment response. ConclusionsA poor treatment outcome for patients with the 4 R homozygosity had presented,that comparing with those DRD non-4/4 genotype carriers. DRD4 VNTR 4 R homozygosity could be a genetic biomarker to predict poor antipsychotic treatment response in schizophrenia. Patients with DRD 4/4 probably receive novel antipsychotic medications preferentially or in combination with alternative therapy, such as psychotherapy or milieu therapy.

Association of IL-1β rs16944 and IL-1RN rs2234663 gene polymorphisms with graft function in renal transplant recipients

BackgroundAfter renal transplantation, renal graft function affects both patient and graft survival. There is growing evidence of the genetic association between interleukin-1β (IL-1β) or its receptor antagonist (IL-1RN) and graft function in renal transplantation. The objective of this study is to investigate the role of the recipient IL-1β and IL-1RN gene polymorphisms and their haplotypes on renal graft outcome.MethodsUsing PCR, IL-1β (− 511C/T) and IL-1RN (86 bp VNTR) gene polymorphisms were determined in 31 renal allograft recipients; eight cases with stable allograft function and 23 cases with early renal dysfunction as well as 26 age- and gender-matched healthy controls.ResultsA statistically significant difference in IL-1 β (− 511C/T) gene polymorphisms and IL-1RN/IL-1β haplotypes was observed on comparing renal allograft recipients with stable allograft function and those with early renal allograft dysfunction. However, the difference in the frequency distribution of IL-1RN gene polymorphisms, between these two groups, did not reach statistical significance. Also, no statistically significant difference was observed in comparing these two gene polymorphisms and their haplotypes between renal allograft recipients and healthy controls.ConclusionThe IL-1β − 511 CT/TT polymorphic genotypes and IL-1RN/IL-1β polymorphic haplotypes are associated with early renal allograft dysfunction. These are observational data that can be repeated in larger studies. If the results obtained are consistent, this might open doors to personalized medicine where clinicians can take necessary measures to identify the renal transplant recipients’ genotypes at risk of mounting an increased inflammatory response and hence administer the appropriate immunosuppressive protocol.

Investigating the relationship between the VNTR variant of the interleukin-1 receptor antagonist gene and coronary in-stent restenosis.

This study aimed to examine the association between the interleukin-1 receptor antagonist gene (IL-1RN) and coronary in-stent restenosis (ISR) through the analysis of the VNTR variant based on the previously reported results. The samples were classified into two clearly defined groups: the case group, which comprised 45 patients diagnosed with in-stent restenosis (ISR+), and the control group, which included 60 patients without ISR (ISR-). Polymerase chain reaction (PCR) was performed to examine the 86-bp VNTR variant of the IL-1RN gene. In the analysis of six identified groups consisting of variant alleles of 86 base pairs of VNTR of the IL-1RN gene statistically significant difference was observed for the presence of IL1RN*2 allele between cases and controls (p = 0.04, OR; 0.045). Individuals with allele 2 of the IL-1Ra gene may be more predisposed to ISR. This could be due to an imbalance between IL-1Ra and IL-1β which is crucial in preventing the initiation or advancement of inflammatory diseases in specific organs. The observed phenomenon can be characterized by increased production of IL-1β and potential reduction of IL-1Ra as a result of functional VNTR variation in IL-RN gene.

Genetic biomarkers for risk prediction of chronic obstructive pulmonary disease (COPD) in smokers and non-smokers

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease and not fully reversible. It is the 3rd major cause of death worldwide and ranks 2nd in India. Although the primary etiopathogenic factor is chronic exposure to tobacco smoke, it has been observed that all smokers do not develop COPD and many non-smokers suffer from the disease. This difference in susceptibility can be attributed to individual genetic variations. Therefore, the present study was conducted to analyze the association of genetic variants in candidate genes with COPD susceptibility among smokers and non-smokers. A total of 500 subjects were enrolled in the study (250 each of controls and cases) after ethical approval and informed consent. Fifteen single nucleotide polymorphisms (SNPs) in eight genes viz.IL-1RN, IL-1B, IL-6, TNF-A, SOD2, CAT, ADAM33 and AQP5 were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR–RFLP). Data was analyzed using SPSS (ver 21.0) and association with smoking status was determined. Among 250 healthy controls enrolled, 119 were non-smokers and 131 were smokers. Out of 250 COPD cases, only 34 were non-smokers and rest 216 were smokers. The genotypic frequencies of IL-1RN intron2 86 bp VNTR (I,II), IL-1β -511 T/C, IL-6 -597A/G, TNF-α -308G/A, SOD2 + 47C/T, CAT − 21A/T and AQP5 promoter G/A were significantly associated with smoking. Among 07 ADAM33 SNPs, the genotype frequencies of V4exon22C/G and F + 1intron6C/T were significantly associated in smokers, while V1exon22G/T, S2exon19G/C, S1exon19A/G and Q1intron16A/G were associated with non-smokers. The genetic variants (SNPs) in smokers and non-smokers showing differential association with the risk of COPD can be identified as predictive biomarkers.

Genetic Polymorphisms Are Differentially Associated With Affective Outcomes in Adolescents With and Without ADHD

AimsVarious genetic polymorphisms have been associated with attention-deficit/hyperactivity disorder (ADHD), and some of these have also been implicated in individual differences in affective processing. Yet, no studies to date have examined the complex interrelations across these genetic polymorphisms, ADHD, and affective processing. Several variables (e.g., age, ethnicity, sex) have been shown to affect whether a given genetic variant confers risk. Our aim was to examine whether relevant genetic variants differentially confer risk for negative affectivity (NA) and/or emotion dysregulation (ED), depending on ADHD status.MethodsParticipants were n = 297 adolescents (Mage=15.30 years; SD = 1.06; 60.27% boys) with (n = 83) and without (DSM-5) ADHD. ADHD- and affective processing-related dopaminergic and serotonergic polymorphisms were genotyped (i.e., DRD2/ANKK1 TaqIA (rs1800497), dopamine receptor DRD4 exon-3 48 bp VNTR, and serotonin transporter linked polymorphic region 5-HTTLPR including the rs25531). Affectivity and ED were measured via parent- and/or self-report.ResultsWe first calculated bivariate correlations between polymorphisms, affectivity, and ED then compared the obtained (Fisher's r to z-transformed) values between with and without ADHD groups. There were no correlations that were significant – but several differed – across groups. In youth without ADHD, carrying the DRD2 rs1800497 T-allele was negatively associated both with negative affectivity (pcorr=.033) and with self-rated ED (pcorr=0.039). In youth with ADHD, carrying the DRD4 VNTR 7-repeat allele was positively associated with self-rated ED (pcorr=0.008), and carrying the L'L’ relative to the low-expression S’ serotonergic allele was also positively associated with parent-rated ED (pcorr=.042)ConclusionDifferences across with and without ADHD groups with regard to correlations between genetic polymorphisms - previously implicated in both ADHD and affective processing - and negative affectivity and emotion dysregulation indicate that certain genetic variants may differentially confer risk for affective outcomes, given ADHD status. These results have implications for targeted prevention of adolescent affective outcomes, which will be discussed during the presentation. That findings held across different indices of affective processing (dispositional affectivity and certain emotion dysregulation components) suggest these results may be robust.

Genetic studies of nephrotic syndrome in Egyptian children

Nephrotic syndrome (NS) might be caused by a kidney disorder or it can be a secondary disease. Untreated or resistant to treatment, NS stimulates glomerular damage that reduces the kidney function. This reduction leads to the end stage of renal failure. Therefore, it is very important to diagnose NS early, with the aim of inhibiting or lessening its associated morbidity and mortality. Gene polymorphism analysis for the three genes eNOS 27 bp VNTR, GSTP1 and IL-10(1082 G/A) were checked in 98 children with NS and 101 control subjects. eNOS 27 bp VNTR genotypes and alleles are significantly different in the group of 98 children with NS compared to the 101 control subjects. The frequencies of ab and bb genotypes are significantly lower in patients than in the control group (ab: 17.2% vs. 22.8%; OR: 0.19; 95% CI: 0.06-0.58; p = 0.0026 & bb: 54.7% vs. 70.3%; OR: 0.19; 95% CI: 0.07-0.5; p = 0.0004). However, neither GSTP1 nor IL-10(1082 G/A) genotypes showed any significant difference in both groups. eNOS 27 bp VNTR gene might be considered as an independent risk factor in the early prediction of nephrotic syndrome incidence, which may help prevent/reduce the occurrence of other complications associated with the late diagnosis and treatment of the disease.

Interleukin 4 and Interleukin 4 receptor alpha gene variants and risk of atopy - A case control study based assessment

IntroductionIL4 pathway is known to upregulate IgE mediated immune responses and responsible for the manifestation of Atopic disorders. The current study was aimed to elucidate the genetic variations of Interleukin 4 (IL4) and Interleukin 4 receptor alpha (IL4R) genes and their possible association with atopic subjects. MethodsThe well-designed questionnaire was used to collect the subject demographic and clinical details. Biochemical parameters were analysed using Chemiluminescent Immunoassay (CLIA) technique. The genotyping was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). ResultsWe observed a statistically significant difference of serum Immunoglobulin-E (IgE) levels among cases and controls (P<0.05). Subjects harbouring the variant genotypes of I50V and Q576R single nucleotide polymorphisms (SNPs) in IL4R gene showed statistically differential risk towards atopic disorders. However, the variants genotype of 70 bp VNTR polymorphism in IL4 gene showed a protective role towards in predisposition to Atopy. On stratification, the above genetic variants had a significant impact on modifiable and non-modifiable factors associated with the disease. ConclusionOur study demonstrates that increased IgE levels and IL4 gene variants (I50V and Q576R) are significantly associated towards predisposition to allergic disorders in this study population.

SLC6A3 (DAT1) as a Novel Candidate Biomarker Gene for Suicidal Behavior.

It has been previously shown that the serotonin and dopamine neurotransmitter systems might influence the predisposition to suicidal behavior. This study aims to estimate the contribution of 11 polymorphisms in the genes SLC6A4 (5HTT), HTR1A, HTR2A, HTR1B, SLC6A3 (DAT1), DRD4, DRD2, COMT, and BDNF to suicidal behavior and severity of symptoms of depression and anxiety in the Russian population. The study was performed on 100 patients with repeated suicide attempts and 154 controls. We first found an association between SLC6A3 (DAT1) 40 bp VNTR locus and suicidal behavior. This association was significant; when using the codominant (p = 0.006), dominant (p = 0.001), overdominant (p = 0.004), and log-additive (p = 0.004) models, LL genotype played a protective role (OR = 0.48, 0.29–0.82, p = 0.005). Difference in the distribution of COMT rs4680 genotypes was significant in the codominant (p = 0.04), dominant (p = 0.013), and log-additive (p = 0.02) models, and AA genotype might protect against suicide (OR = 0.49, 0.26–0.91, p = 0.025). SLC6A4 5-HTTLPR + rs25531 locus was significant in the recessive model (p = 0.024), and also affected the severity of symptoms of depression (p = 0.044) and personal anxiety (p = 0.029). Our results suggest that allelic variants of SLC6A3, COMT, and SLC6A4 genes might be considered as risk factors for suicidal attempts.

Association Between Endothelial Nitric Oxide Synthase (eNOS) -786 T/C and 27-bp VNTR 4b/a Polymorphisms and Preeclampsia Development.

The aim of the present study was to analyze the distribution of genotypes and haplotypes of functional eNOS gene polymorphisms in the promoter (-786 T/C), intron 4 (VNTR4b/a) and exon 7 (894 G/T), in Serbian population of pregnant women, and establish a possible association between these polymorphisms and preeclampsia development. DNA was isolated from venous blood samples of 50 heathy pregnant women and 50 preeclampsia patients. Polymerase Chain Reaction/Restriction Fragment Length Polymorphism (PCR/RFLP) technique, with appropriate sets of primers and specific restriction enzymes, was used to determine polymorphisms in eNOS gene. Statistical analysis was done using the SPSS and HAPLOVIEW software packages. eNOS -786 T/C polymorphism was significantly associated with preeclampsia (P = 0.006). Homozygotes for the VNTR polymorphism had also an elevated risk of developing preeclampsia (OR=7.68, 95%CI (0.89-65.98)), especially the mild (OR=9.33, 95%CI (0.98-88.57)) and late form (OR=8.52, 95%CI (0.90-80.58)). The 894 G/T polymorphism was not associated with preeclampsia. "G-C-b" and "T-4a-T" haplotypes were more frequent in preeclampsia, though without reaching statistical significance. -786 T/C and VNTR 4b/a eNOS gene polymorphisms were associated with preeclampsia risk in Serbian patients.

The presence of polymorphisms in genes controlling neurotransmitter metabolism and disease prognosis in patients with prostate cancer: a possible link with schizophrenia.

Polymorphisms of neurotransmitter metabolism genes were studied in patients with prostate cancer (PC) characterized by either reduced or extended serum prostate-specific antigen doubling time (PSADT) corresponding to unfavorable and favorable disease prognosis respectively. The ‘unfavorable prognosis’ group (40 cases) was defined by PSADT ≤ 2 months, whereas patients in the ‘favorable prognosis’ group (67 cases) had PSADT ≥ 30 months. The following gene polymorphisms known to be associated with neuropsychiatric disorders were investigated: a) the STin2 VNTR in the serotonin transporter SLC6A4 gene; b) the 30-bp VNTR in the monoamine oxidase A MAOA gene; c) the Val158Met polymorphism in the catechol-ortho-methyltransferase COMT gene; d) the promoter region C-521T polymorphism and the 48 VNTR in the third exon of the dopamine receptor DRD4 gene.The STin2 12R/10R variant of the SLC6A4 gene (OR = 2.278; 95% CI = 0.953–5.444) and the -521T/T homozygosity of the DRD4 gene (OR = 1.579; 95% CI = 0.663–3.761) tended to be overrepresented in PC patients with unfavorable disease prognosis. These gene variants are regarded as protective against schizophrenia, and the observed trend may be directly related to a reduced PC risk described for schizophrenia patients. These results warrant further investigation of the potential role of neurotransmitter metabolism gene polymorphisms in PC pathogenesis.

Association of DRD4 exon III and 5-HTTLPR VNTR genetic polymorphisms with psychiatric symptoms in hemodialysis patients.

Mental illness is prevalent among hemodialysis (HD) patients. Given that the dopaminergic and serotonergic pathways are involved in the etiology of psychiatric disease, this study evaluated the genetic association of dopamine D4 receptor (DRD4) and serotonin transporter (SLC6A4) genes with psychiatric symptom susceptibility among HD patients. Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depressive symptoms among patients (n = 265). Genetic polymorphisms of DRD4 (48 bp VNTR) and SLC6A4 (5-HTTLPR VNTR and rs25531) were examined using a conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, as appropriate. Significant differences were observed in the distribution of 5-HTTLPR genotypes, SLC6A4 tri-allelic-phased genotype, and DRD4-Exon III VNTR genotypes/alleles between patients with anxiety symptoms versus those with normal/borderline conditions (p<0.05). Binary logistic regression analyses showed that the heterozygous 4,5 VNTR genotype of DRD4 was associated with a higher risk of anxiety symptoms after adjusting for other covariates (odds ratio = 4.25, p = 0.028). None of the studied polymorphisms was linked to depression in HD patients. Collectively, the current findings provide genetic clues to psychopathology in HD patients and suggest that the DRD4 exon III VNTR polymorphism is involved in the etiology of anxiety in this patient population.

Dopamine D4 receptor gene polymorphism (DRD4 VNTR) moderates real-world behavioural response to the food retail environment in children

BackgroundEvidence for the impact of the food retailing environment on food-related and obesity outcomes remains equivocal, but only a few studies have attempted to identify sub-populations for whom this relationship might be stronger than others. Genetic polymorphisms related to dopamine signalling have been associated with differences in responses to rewards such as food and may be candidate markers to identify such sub-populations. This study sought to investigate whether genetic variation of the dopamine D4 receptor gene (DRD4 exon III 48 bp VNTR polymorphism) moderated the association between local exposure to food retailers on BMI and diet in a sample of 4 to12-year-old children.MethodsData collected from a birth cohort and a community cross-sectional study conducted in Montreal, Canada, were combined to provide DRD4 VNTR polymorphism data in terms of presence of the 7-repeat allele (DRD4-7R) for 322 children aged between 4 and 12 (M (SD): 6.8(2.8) y). Outcomes were Body Mass Index (BMI) for age and energy density derived from a Food Frequency Questionnaire. Food environment was expressed as the proportion of local food retailers classified as healthful within 3 km of participants’ residence. Linear regression models adjusted for age, sex, income, cohort, and geographic clustering were used to test gene*environment interactions.ResultsA significant gene*food environment interaction was found for energy density with results indicating that DRD4-7R carriers had more energy dense diets than non-carriers, with this effect being more pronounced in children living in areas with proportionally more unhealthy food retailers. No evidence of main or interactive effects of DRD4 VNTR and food environment was found for BMI.ConclusionsResults of the present study suggest that a genetic marker related to dopamine pathways can identify children with potentially greater responsiveness to unhealthy local food environment. Future studies should investigate additional elements of the food environment and test whether results hold across different populations.

Fluoride exposure, dopamine relative gene polymorphism and intelligence: A cross-sectional study in China

BackgroundExcessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children’s intelligence remain unclear. ObjectivesWe conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. MethodsWe recruited 567 resident children, aged 6–11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. ResultsIn adjusted model, fluoride exposure was inversely associated with IQ scores (β = −5.957, 95% CI: −9.712, −2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). ConclusionsOur study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.

A Relationship between Endothelial Nitric Oxide Synthetase Gene Variants and Substance Use Disorder.

Addictive substances are known to result in oxidative stress (OS). OS enhances the generation of free radicals and reactive oxygen species (ROS) and reduces antioxidant capacity. Peroxides and oxygen radicals, including hydrogen peroxide and superoxide and radical nitrogen species, including nitric oxide (NO), are parts of the ROS. Gene variants of the endothelial nitric oxide (eNOS) affect the plasma levels of NO. This study aimed to investigate whether there was an association between eNOS variants and substance use disorders (SUDs) risk in the Turkish population. Two eNOS variants (G894T and 27 bp VNTR 4b/a in intron 4) were examined in 216 SUD patients and 140 healthy controls. The eNOS variants were assessed with the PCR based on the RFLP analysis. Since the patient group consisted only of men, the control group was examined as a mixed and male-only. The eNOS G894T homozygous T/T genotype revealed a significant association with susceptibility to SUD. The patients carrying T/T genotype had SUD risk 1.054 times as much as the controls and male controls had (p=0.004 and p=0.038, respectively). eNOS 4a/4a genotype increased in patients as compared to male controls (p=0.048). The homozygous 4b/4b genotype was higher in the male control group than in SUD patients (p=0.029). eNOS VNTR 4a allele was more prevalent in the patients than in both controls and male controls (p=0.026 and p=0.0033, respectively). This study is one of the first studies investigating the relationship between two eNOS gene variants and SUD in our country. Our findings show that eNOS G894T and VNTR variants may be the significant risk factor for SUDs in Turkish subjects.

Dopamine transporter availability in alcohol and opioid dependent subjects – a 99mTc-TRODAT-1SPECT imaging and genetic association study

Drug dependence associated with increased dopamine neurotransmission and neuroplastic changes is influenced by Dopamine transporters (DAT) which are modulated by genetic and epigenetic factors. This study assesses DAT availability in relation to the 40bp DAT1 VNTR (genetic) and DAT1 promoter methylation (epigenetic) changes in patients with alcohol dependence (AD) and opioid dependence (OD). A total of 60 subjects (n=20 each of AD, OD and controls) were recruited. SPECT/CT imaging using 99mTc-TRODAT-1 was performed for measuring striatal DAT availability and DNA screened to check DAT1promoter methylation and 40bp VNTR polymorphism. SPECT/CT imaging revealed significant decrease in DAT availability in the striatum and putamen and significant increase in DAT1 promoter methylation in AD compared to control and OD. The 40bp VNTR distribution was similar in all three groups with 10repeat and 9repeat alleles being the most common. The AD individuals with DAT1promoter methylation showed significantly lower TRODAT-1 uptake compared to the ones with no methylation. AD individuals homozygous for the 10repeat VNTR also showed reduced DAT availability. This is the first imaging study using 99mTc-TRODAT-1 from India documenting significantly reduced striatal DAT availability, increased DAT methylation and frequency of 10repeat individuals associated with decreased DAT availability in AD.

Association of DRD2 Gene Ser311Cys Polymorphisms, DAT 40bp VNTR and Cannabis Dependence

Cannabis as the most widely used illicit drugs among Nigerians has been associated with psychiatric disorders. Studies have implicated genetic predisposition in drug abuse and dependence. We therefore aimed at finding out the relationship between some dopaminergic gene polymorphisms and cannabis dependence.One hundred and four patients attending a psychiatric facility in Lagos, Nigeria who were diagnosed of cannabis dependence according to ICD‐10 were recruited for the study. Ninety six subjects who were not smoking cannabis were also recruited as a comparative group. Genotyping was carried out for Ser311Cys polymorphism of the dopamine receptor D2 (DRD2) gene and the 40bp VNTR of the dopamine transporter (DAT) gene.The Cys allele was more frequent than the Ser allele among the smokers (0.878 and 0.122 respectively), compared to the non‐smokers (0.611 and 0.389 respectively). Most of the smokers were homozygous Cys/Cys (0.433) while most of the non‐smokers were heterozygous Ser/Cys (0.798). Individuals with DRD2 Ser311 allele were more than five times as likely to use cannabis as those with Cys311(p = 0.001, OR = 4.575, 95%CI = 2.727–7.678). The 9 and 10‐repeats (9R and 10R) of the DAT VNTR were the most common repeats. Other repeats were very few and were even found in heterozygous form in combination with either 9 or 10 repeats. The 10R allele was more frequent than the 9R among the smokers (0.560 and 0.440 respectively) and also among the non‐smokers (0.726 and 0.274). While most of the smokers were heterozygous 9R/10R (0.559), most non‐smokers were homozygous 10R/10R (0.595). Individuals with at least one 10R were almost twice as likely to use cannabis as those with the 9R (p = 0.004, OR = 1.915, 95%CI = 1.225 – 2.995).The Cys311 allele of the DRD2 and the 10R of the DAT VNTR were significantly associated with cannabis smoking as individuals with these alleles were more likely to smoke cannabis.

Association of SLC6A3 gene polymorphisms with the pharmacokinetics of Levodopa and clinical outcome in patients with Parkinson’s disease

Levodopa (LD) is the gold standard for the treatment of Parkinson’s disease (PD). Genetic polymorphisms in the SLC6A3 gene (Solute carrier family 6 member 3/DAT-Dopamine Transporter gene) are shown to have a functional impact on levodopa therapeutic response, motor complications of PD and adverse events. Hence the present study was carried out to investigate the association of SLC6A3 polymorphisms with the pharmacokinetics of levodopa and clinical response. A total of 150 PD patients were recruited in the study. Plasma levodopa was analysed by HPLC at 0, 1, 2, 3 and 4 h post levodopa administration and AUC was calculated. Genotyping of SLC6A3 40 bp VNTR and SLC6A3 rs393795 (G>T) polymorphisms was done by the PCR-RFLP method. The result shows that AUC of levodopa was significantly higher in patients carrying homozygous10/10 genotype (P =0008) compared to 9/9 genotype of SLC6A3 40 bp VNTR polymorphism. A similar difference was also observed in early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD) groups. SLC6A310/10 genotype was found to be significantly associated with disease severity (P =0.05) compared with the 9/10 genotype in the EOPD group, however, there was no significant association with dyskinesia. To conclude, patients carrying SLC6A3 40VNTR 10/10 genotype were found to have higher levodopa exposure, disease severity and prone to further neurodegeneration.

A Meta-analysis of the Association Between SLC6A3 Gene Polymorphisms and Schizophrenia.

The dopamine transporter is coded by the SLC6A3 gene and plays an important role in regulation of the neurotransmitter dopamine. To detect the association between the SLC6A3 gene and the risk of schizophrenia, 31 case-control articles were included in this meta-analysis. There were 23 studies with 40bp VNTR (3246 cases and 3639 controls), 4 studies with rs40184 (2020 cases and 1674 controls), rs6347 (1317 cases and 1917 controls), rs403636 (2045 cases and 1704 controls), and rs2975226 (849 cases and 904 controls); and 3 studies with rs12516948 (1920 cases and 1569 controls), rs27072 (984 cases and 1015 controls), rs6869645 (1142 cases and 1082 controls), rs37022 (1168 cases and 1091 controls), rs464049 (1169cases and 1096 controls), rs2652511 (707 cases and 714 controls), and rs3756450 (1176 cases and 1096 controls). Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. In the dominant genetic model, the genotype AA+AT of rs2975226 in the Indian population (Pz = 0, odds ratio [OR] = 3.245, 95% confidence interval [CI] = 1.806-5.831), TT of rs464049 (Pz = 0.002, OR = 1.389, 95% CI = 1.129-1.708), and TT of rs3756450 (Pz = 0.014, OR = 1.251, 95% CI = 1.047-1.495) might be risk factors for schizophrenia. Additionally, no other single nucleotide polymorphisms were observed. These results indicate that more functional studies are warranted.

The influence of genetic factors on personality and coping with stress among healthy late reproductive age women.

BackgroundPsychological stress is a factor which predisposes people to many somatic and mental disorders. Women are at a significantly higher risk of stress than men, and their reactions to stress are stronger. Personality traits are thought to play a special role in the psychology of stress and may be crucial for the choice of a stress-coping strategy. Considering that stress is so common in everyday life, an attempt to understand how stress-coping styles are related to personality and genetic factors acquires special significance.PurposeThe aim of this study was to analyze stress-coping styles and personality traits in healthy late reproductive age women with regard to genetic factors.Patients and methodsThe study involved 345 healthy late reproductive age women from northwest Poland, whose mean age was 42.3±4.5 years. The study was conducted using The Coping Inventory for Stressful Situations, The Neuroticism-Extraversion-Openness Five--Factor Inventory, and genetic testing.ResultsThere were neither statistically significant relationships between personality traits and the genotype distribution of the 30-bp VNTR polymorphism in the MAO-A promoter region, nor between stress-coping styles and the genotype distribution of the 30-bp VNTR polymorphism in the MAO-A promoter region.ConclusionBased on the results, all personality traits statistically significantly correlated with the choice of task-oriented coping and emotion-oriented coping. Some of personality traits are genetically determined. The choice of a stress-coping style was significantly related to personality traits. A direct influence of genetic factors on the choice of a stress-coping style was not confirmed in our study.