Rhesus Macaques: VNTR Polymorphism of the FCGRT Gene.

Variable number tandem repeat (VNTR) polymorphisms of the human neonatal IgG Fc receptor α-chain gene (FCGRT) are known to influence the expression levels of FCGRT and IgG in serum. Monkeys are considered to be a relevant biological model for studying the effects of immunobiological drugs. The study determined the functional VNTR polymorphisms of the FCGRT gene in 109 male rhesus macaques from the nursery of the Kurchatov Complex of Medical Primatology. PCR amplification of samples was carried out followed by electrophoretic separation of DNA fragments in a 2% agarose gel. Individual DNA amplification products were sequenced (according to Sanger system) in forward and reverse directions to confirm the specificity. The genotyping showed that the VNTR polymorphism of the FCGRT gene in the studied population of rhesus macaques is presented by 9 variants. The frequency of the VNTR5 allele associated with lower IgG levels was 14.2%, and the most common one was the VNTR7 allele (25.2%). We also identified alleles that have not been previously reported: VNTR3, VNTR4, VNTR6, VNTR8, and VNTR9. The study allows to consider rhesus macaques as a potential model for studying the immunological response depending on the genetic VNTR variant of FCGRT.

Exploring the Relationship between CLPTM1L-MS2 Variants and Susceptibility to Bladder Cancer.

CLPTM1L (Cleft Lip and Palate Transmembrane Protein 1-Like) has previously been implicated in tumorigenesis and drug resistance in cancer. However, the genetic link between CLPTM1L and bladder cancer remains uncertain. In this study, we investigated the genetic association of variable number of tandem repeats (VNTR; minisatellites, MS) regions within CLPTM1L with bladder cancer. We identified four CLPTM1L-MS regions (MS1~MS4) located in intron regions. To evaluate the VNTR polymorphic alleles, we analyzed 441 cancer-free controls and 181 bladder cancer patients. Our analysis revealed a higher frequency of specific repeat sizes within the MS2 region in bladder cancer cases compared to controls. Notably, 25 and 27 repeats were exclusively present in the bladder cancer group. Moreover, rare alleles within the medium-length repeat range (25-29 repeats) were associated with an elevated bladder cancer risk (odds ratio [OR] = 5.78, 95% confidence interval [CI]: 1.49-22.47, p = 0.004). We confirmed that all MS regions followed Mendelian inheritance, and demonstrated that MS2 alleles increased CLPTM1L promoter activity in the UM-UC3 bladder cancer cells through a luciferase assay. Our findings propose the utility of CLPTM1L-MS regions as DNA typing markers, particularly highlighting the potential of middle-length rare alleles within CLPTM1L-MS2 as predictive markers for bladder cancer risk.

Molecular Evaluation of Ex3 VNTR Polymorphism of the DRD4 Gene in Patients With Autism Spectrum Disorder.

Objective: Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders that affect social and communication skills. These diseases are characterized by severe communication and social skills disabilities and limited and repetitive activities. The prevalence of these disorders appears to be steadily increasing. It is proposed that the genes involved in the dopamine pathway may play an essential role in the development of autism. In this study, we investigated the possible association between Ex3 VNTR polymorphism of the DRD4 gene and autism spectrum disorders in the Iranian population. Materials & Methods: In this case-control study, 97 children with autism and 103 healthy individuals from a northwestern area of Iran as the case and control groups, respectively. After genomic xtraction from peripheral blood samples by the proteinase K method, the polymerase chain reaction (PCR) technique was used to determine the polymorphism genotypes. The data were then coded and analyzed using SPSS version 22 software. Results: The study results showed that the allele frequencies differed in the two groups, some of them being statistically significant. The most common allele in both the ASD and the control group was the 700 bp allele, and its frequency was significantly different in the two groups and was more common in the ASD group (p-value=0.0018). The other allele with a statistically different frequency was the 800 bp allele which was less frequent in the ASD group (p-value=0.0017). Conclusion: These results suggest a potential association between Ex3 VNTR polymorphism of the DRD4 gene and autism spectrum disorder in the Iranian population. This necessitates further studies for the evaluation of the DRD4 gene.

Dim light melatonin onset following simulated eastward travel is earlier in young males genotyped as PER35/5 than PER34/4.

Inter-individual variability exists in recovery from jetlag following travel across time zones. Part of this variation may be due to genetic differences at the variable number tandem repeat (VNTR) polymorphism of the PERIOD3 (PER3) gene as this polymorphism has been associated with chronotype and sleep, as well as sensitivity to blue light on melatonin suppression. To test this hypothesis we conducted a laboratory-based study to compare re-entrainment in males genotyped as PER34/4 (n = 8) and PER35/5 (n = 8) following simulated eastward travel across six time zones. The recovery strategy included morning blue-enriched light exposure and appropriately-timed meals during the first 24 h after simulated travel. Dim light melatonin onset (DLMO), sleep characteristics, perceived sleepiness levels (Stanford Sleepiness Scale), and resting metabolic parameters were measured during constant routine periods before and after simulated travel. While DLMO time was similar between the two groups prior to simulated eastward travel (p = .223), it was earlier in the PER35/5 group (17h23 (17h15; 17h37)) than the PER34/4 group (18h05 (17h53; 18h12)) afterwards (p = .046). During resynchronisation, perceived sleepiness and metabolic parameters were similar to pre-travel in both groups but sleep was more disturbed in the PER35/5 group (total sleep time: p = .008, sleep efficiency: p = .008, wake after sleep onset: p = .023). The PER3 VNTR genotype may influence the efficacy of re-entrainment following trans-meridian travel when blue-enriched light exposure is incorporated into the recovery strategy on the first day following travel.

Association between interleukin-1 receptor antagonist (IL-1ra) VNTR, gene polymorphism and breast cancer susceptibility in Iranian population: Experimental and web-based analysis.

Breast cancer is one of the leading causes of cancer mortality. Growing evidence indicates that interleukins and its polymorphisms are involved in the pathogenesis of breast cancer. Variable number of tandem repeat (VNTR) polymorphism can affect transcription rate, mRNA stability and also the resulting protein expression and activity. Hence, present study aimed to assess the possible association between interleukin-1 receptor antagonist (IL-1Ra) VNTR polymorphism, and breast cancer susceptibility in Iranian population. A total of 300 Iranian individuals, 150 breast cancer patients and 150 age-matched healthy women, were included in this study. DNA extracted by salting out method and genotyping was done using the polymerase chain reaction. The frequency of the allele 2(5% vs. 22%) and the 2/2 genotype (22% vs. 46%) of IL-1Ra VNTR polymorphism was significantly higher in healthy control compared to breast cancer patient: therefore, A2 allele may play a protective role against breast cancer and its progression (p = .0001 and OR = 0.105, 95% CI: [0.044-0.248]). The allele 2 and 2/2 genotype of the IL-Ra VNTR polymorphism can be a protective factor against breast cancer susceptibility.

Effect of VNTR Polymorphism of the AS3MT Gene and Obstetrical Complications on the Severity of Schizophrenia.

The role of the VNTR polymorphism of the AS3MT gene in determining the clinical features of schizophrenia and schizophrenic spectrum disorders was studied. The analysis included 670 individuals. We found no differences in PANSS scores for positive, negative, and common psychopathological symptoms between the carriers of different genotypes. The interaction of the studied polymorphism and obstetrical complications as an environmental factor was found. The genotype-environment interactions were identified for one of the characteristics reflecting the severity of schizophrenia: the level of negative symptoms. Women with the V2/V2 genotype, who have obstetrical complications, showed significantly higher negative symptoms scores, which was associated with a poor prognosis of the disease.

Dopamine transporter genotype modulates brain activity during a working memory task in children with ADHD.

Dopamine active transporter gene (DAT1) is a candidate gene associated with attention-deficit/hyperactivity disorder (ADHD). The DAT1 variable number tandem repeat (VNTR)-3' polymorphism is functional and 9R carriers have been shown to produce more DAT than 10R homozygotes. We used functional magnetic resonance imaging (fMRI) to investigate the effects of this polymorphism on the neural substrates of working memory (WM) in a small but selected population of children with ADHD, naïve of any psychotropic treatment and without comorbidity. MRI and genotype data were obtained for 36 children (mean age: 10,36 +/- 1,49 years) with combined-type ADHD (9R n = 15) and 25 typically developing children (TDC) (mean age: 9,55 +/- 1,25 years) (9R n = 12). WM performance was similar between conditions. We found a cross-over interaction effect between gene (9R vs. 10R) and diagnosis (TDC vs. ADHD) in the orbito-frontal gyrus, cerebellum and inferior temporal lobe. In these areas, WM-related activity was higher for 9R carriers in ADHD subjects and lower in TDC. In ADHD children only, 10R homozygotes exhibited higher WM-related activity than 9R carriers in a network encompassing the parietal and the temporal lobes, the ventral visual cortex, the orbito-frontal gyrus and the head of the caudate nucleus. There was no significant results in TDC group. Our preliminary findings suggest that DAT1 VNTR polymorphism can modulate WM-related brain activity ADHD children.

Positive correlation between interleukin-1 receptor antagonist gene 86bp VNTR polymorphism and colorectal cancer susceptibility: a case-control study.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Genetic variations in cytokine genes and their receptors lead to the severity of the disease. The interleukin-1 receptor antagonist (IL1RN) is a cytokine that inhibits interleukin-1 (IL-1) activity by binding to IL-1 receptors. Also, interleukin-4 (IL-4) is an anti-inflammatory cytokine that can play an important role in several cancers. The present case-control study was aimed to evaluate the association of IL-4 and IL1RN VNTR polymorphisms with the susceptibility to CRC in a sample of Iranian population provided by the Research Center for Gastroenterology and Liver Disease at Taleghani Hospital, Tehran. A total of 123 patients diagnosed with CRC and 152 healthy controls were recruited in the present study. Genomic DNA was extracted by salting out method from whole blood and genotyping of IL1RN and IL-4 VNTR polymorphisms were determined by PCR-based technology. Our study manifested the frequency of 1/2 and 2/4 genotypes of IL1RN 68bp VNTR polymorphism are significantly different between both groups (p = 0.0001 and p = 0.01 respectively). However, we could not find any correlation between IL-4 VNTR polymorphism and CRC cancer. It seems that 1/2 and 2/4 genotypes of IL1RN are correlated with CRC susceptibility in our population, although, more studies are needed to confirm our results.

IL4 gene VNTR polymorphism in chronic periodontitis in end-stage renal disease patients.

OBJECTIVE: Interleukin-4 gene polymorphisms were found to be associated with periodontitis. The purpose of this case-control study was to evaluate association of IL4 VNTR polymorphism with periodontitis in patients with end-stage renal disease (ESRD). SUBJECTS AND METHODS: We examined 180 ESRD patients with chronic periodontitis, 82 without CP and 180 healthy controls. Genomic DNA from all subjects was genotyped for the IL4 VNTR polymorphism by polymerase chain reaction (PCR). RESULTS: Genotype distribution in all groups followed Hardy-Weinberg equilibrium. Significant differences in genotype and allele frequencies were observed between groups. The patient group had higher frequency of P1 allele than controls, with odds ratio for P1 allele 1.6 (95% CI 1.1-2.3) and P1P1 genotype 2.73 (95% CI 1.06-7.5). There were no differences in polymorphism distribution between ESRD patients without CP and controls. Periodontal disease was more severe in older patients (≥50 years). Similarly, patients with T2DM had more severe manifestation of CP than patients without diabetes (p = 0.01 for plaque index, p = 0.004 for bleeding index and p = 0.03 for gingival index). CONCLUSION: Our findings suggest that VNTR polymorphism in IL4 gene might be a risk factor for chronic periodontitis in patients with ESRD.

Association between interleukin 4 (IL-4) VNTR, gene polymorphism, and breast cancer susceptibility in Iranian population: experimental and web base analysis.

BACKGROUND: Breast cancer (BC) is one of the most common types of cancer and the second leading cause of cancer death among women. Epidemiological studies showed that BC is linked to genetic and environmental factors, and inheritance plays a key role in the pathobiology of this disease. Interleukin 4 (IL-4) is a key differentiation cytokine and is produced by Th2 and activates Th2 development. Hence the current study aimed to assess the possible association between interleukin 4 (IL-4) VNTR polymorphism, and BC susceptibility in a sample of Iranian population. MATERIAL AND METHODS: IL-4 VNTR polymorphism was evaluated in 150 women with BC and 150 age-matched healthy women by polymerase chain reaction method. RESULT: Among 3 possible alleles for IL-4 gene, we only observed 2 alleles. Current findings indicate that RP2/RP2 genotypes can be regarded as potent protective factors against breast cancer (OR = 0.929 [95%CI, 0.929-0.995]). CONCLUSION: Our result showed that the RP2/RP2 genotype of the IL-4 VNTR polymorphism could be a protective factor for BC susceptibility (Tab. 2, Fig. 1, Ref. 46).