Number Tandem Repeat Polymorphism Research Articles

Association of the neonatal Fc receptor promoter variable number of tandem repeat polymorphism with immunoglobulin response in patients with chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease with humoral and cellular autoimmunity causing demyelination of peripheral nerves, commonly treated with intravenous immunoglobulins (IVIg). The neonatal Fc receptor (FcRn), encoded by the FCGRT gene, prevents the degradation of immunoglobulin G (IgG) by recycling circulating IgG. A variable number of tandem repeat (VNTR) polymorphism in the promoter region of the FCGRT gene is associated with different expression levels of mRNA and protein. Thus, patients with genotypes associated with relatively low FcRn expression may show a poorer treatment response to IVIg due to increased IVIg degradation. VNTR genotypes were analyzed in 144 patients with CIDP. Patients' clinical data, including neurological scores and treatment data, were collected as part of the Immune-Mediated Neuropathies Biobank registry. Most patients (n = 124, 86%) were VNTR 3/3 homozygotes, and 20 patients (14%) were VNTR 2/3 heterozygotes. Both VNTR 3/3 and VNTR 2/3 genotype groups showed no difference in clinical disability and immunoglobulin dosage. However, patients with a VNTR 2 allele were more likely to receive subcutaneous immunoglobulins (SCIg) than patients homozygous for the VNTR 3 allele (25% vs. 9.7%, p = 0.02) and were more likely to receive second-line therapy (75% vs. 54%, p = 0.05). The VNTR 2/3 genotype is associated with the administration of SCIg, possibly reflecting a greater benefit from SCIg due to more constant immunoglobulin levels without lower IVIg levels between the treatment circles. Also, the greater need for second-line treatment in VNTR 2/3 patients could be an indirect sign of a lower response to immunoglobulins.

Study of association of endothelial nitric oxide synthase gene intron 4a/b polymorphism in smokers with ischemic heart disease

Background: Endothelial nitric oxide synthase (eNOS) enzyme plays a key role in maintaining optimal cardiovascular health. Furthermore, the literature review suggests the prominence eNOS gene polymorphisms in pathophysiology of ischemic heart disease (IHD). Aim and Objectives: The aim of this study was to evaluate the association of eNOS gene intron 4a/b polymorphism with IHD in smokers. Materials and Methods: Two hundred male patients presenting with IHD and 100 and 27 age-matched healthy males from the same demographic area were recruited for the study. Based on the history of smoking habit (≥20 pack years of smoking), the subjects were further categorized into non-smokers and smokers. All the subjects were analyzed for the eNOS gene 4a/b polymorphism and other relevant parameters. Results: While studying the association of “aa” genotype with smoking in the patient group as well as in control group, there was no significant association observed between smoking behavior and genotype frequencies (for aa vs. ab+bb, odds ratio [OR] 1.5682, 95% confidence interval [CI] 0.6119–4.0191, P = 0.3457) in patient smokers versus patient non-smokers, OR 0.59, 95% CI 0.1349–2.581, P = 0.479 in control smokers versus control non-smokers. Conclusion: Although genotype frequencies for eNOS 4 b/b, eNOS 4 a/b and eNOS 4 a/a and “a” allele frequency differed between IHD patients and controls, it was not statistically significant indicating “a” allele of eNOS intron 4 a/b variable number of tandem repeat polymorphism was not an independent predictor of IHD.

Interleukin-1 receptor antagonist (IL-1RA) and interleukin-4 (IL-4) variable number of tandem repeat polymorphisms in schizophrenia and bipolar disorder: an association study in Turkish population

BackgroundPro-inflammatory/anti-inflammatory cytokine imbalance in cerebrospinal fluid or plasma of schizophrenia (SCZ) and bipolar disorder (BD) patients has been documented over the last decade. We aim to examine the interleukin-1 receptor antagonist (IL-1RA) and IL-4 variable number of tandem repeat (VNTR) polymorphisms in SCZ and BD patients by comparing them with healthy controls.MethodsTwo hundred and thirty-four unrelated patients (127 patients with SCZ, 107 patients with BD) and 204 healthy controls were included. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis. In addition, the polymerase chain reaction technique was used to investigate IL-1RA and IL-4 VNTR polymorphisms.ResultsOur results showed that the distributions of IL-1RA and IL-4 genotype and the allele frequencies of SCZ or BD patients were not significantly different from the healthy control group. IL-1RA allele 2 homozygous genotype and IL-1RA allele 2 frequencies were non-significantly higher among SCZ patients than in controls.ConclusionsOur study indicates that the IL-1RA and IL-4 VNTR polymorphisms are not considered risk factors for developing SCZ and BD among Turkish patients.

Association between dopamine transporter gene (DAT1/SLC6A3) variants and infertility in the Turkish females

Objective Worldwide, approximately 10–15% of couples is affected by infertility and infertility is associated with disturbances in female and/or male reproductive systems. The aim of the current study is to investigate the relationship between DAT1 (SLC6A3) VNTR polymorphism with female infertility. Methods Genomic DNA extractions were performed in 98 fertile and 90 infertile females, 3' untranslated region (3’ UTR) variable number tandem repeat (VNTR) polymorphism of DAT1/SLC6A3 was determined by the use of Polymerase Chain Reaction (PCR) method. Results It has been demonstrated that there was no statistically significant difference between female infertile and fertile groups in the terms of DAT1 genotypes (p > .05). Moreover, there was no significant difference regarding the frequencies of 9R and 10R alleles in infertile and fertile groups (p > .05). Conclusion This is the first study for investigating the relationship between DAT1/SLC6A3 gene polymorphism and infertility in females. Our study contributes to the growing awareness of the relationship between dopaminergic system and female infertility despite no significant differences were reported between infertile females and corresponding fertile subjects in DAT1/SLC6A3 gene.

Interleukin-4 gene intron 3 VNTR polymorphism in adult acute myeloid leukemia

BackgroundThe proliferation of acute myeloid leukemia (AML) blast into the bone marrow microenvironment is controlled by cytokines. Interleukin-4 (IL-4) has recently been discovered to suppress the development and persistence of AML cells selectively. Intron three of the Interleukin-4 (IL-4) gene contains a 70-bp minisatellite region polymorphism that may influence gene transcriptional activity and subsequently affect the production level of IL4. We investigated the IL-4 gene intron three variable number tandem repeat (VNTR) polymorphism as a molecular marker in AML associated with clinical and laboratory variables and a prognostic factor for therapeutic response and disease outcome.ResultsIL-4 gene intron three minisatellite regions polymorphism was assessed in 60 adult AML patients and 60 healthy controls, comparable concerning age and gender, using polymerase chain reaction. Three study marker genotypes were detected in AML patients; P1/P1 (3%), P1/P2 (40%), and P2/P2 (56.7%). The frequency of P2 alleles was significantly more in AML patients than in healthy controls (76.7% versus 25%; P < 0.001). Compared to the heterozygous group and P1/P1 carriers, AML patients with the homozygous P2/P2 genotype had a higher total leucocytic count and increased blast percentages in bone marrow or peripheral blood, besides a lower platelet count. P2P2 genotype was also significantly associated with poor therapeutic response, higher susceptibility to disease recurrence and shorter overall survival and disease-free survival.ConclusionThe IL-4 intron 3 VNTR polymorphism could be included in the molecular risk stratification of AML to predict poor disease. This information can be utilized in incorporating biological therapy into the present therapeutic protocols to enhance chemotherapy regimens’ current low response rates.

The role of the SLC6A3 3\u2019 UTR VNTR in nicotine effects on cognitive, affective, and motor function

RationaleNicotine has been widely studied for its pro-dopaminergic effects. However, at the behavioural level, past investigations have yielded heterogeneous results concerning effects on cognitive, affective, and motor outcomes, possibly linked to individual differences at the level of genetics. A candidate polymorphism is the 40-base-pair variable number of tandem repeats polymorphism (rs28363170) in the SLC6A3 gene coding for the dopamine transporter (DAT). The polymorphism has been associated with striatal DAT availability (9R-carriers > 10R-homozygotes), and 9R-carriers have been shown to react more strongly to dopamine agonistic pharmacological challenges than 10R-homozygotes.ObjectivesIn this preregistered study, we hypothesized that 9R-carriers would be more responsive to nicotine due to genotype-related differences in DAT availability and resulting dopamine activity.MethodsN=194 non-smokers were grouped according to their genotype (9R-carriers, 10R-homozygotes) and received either 2-mg nicotine or placebo gum in a between-subject design. Spontaneous blink rate (SBR) was obtained as an indirect measure of striatal dopamine activity and smooth pursuit, stop signal, simple choice and affective processing tasks were carried out in randomized order.ResultsReaction times were decreased under nicotine compared to placebo in the simple choice and stop signal tasks, but nicotine and genotype had no effects on any of the other task outcomes. Conditional process analyses testing the mediating effect of SBR on performance and how this is affected by genotype yielded no significant results.ConclusionsOverall, we could not confirm our main hypothesis. Individual differences in nicotine response could not be explained by rs28363170 genotype.

Clinical and Genetic Analysis of Psychosis in Parkinson's Disease.

Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson's disease (PDP). We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson's Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies.

Association between monoamine oxidase A promoter polymorphism and the risk of sudden infant death syndrome: a meta-analysis

IntroductionThe etiology of sudden infant death syndrome (SIDS) remains an unsolved problem. The aim of this meta-analysis is to investigate the potential association between monoamine oxidase A (MAOA) promoter variable number tandem repeat (VNTR) polymorphism and SIDS risk.MethodsA systematic review and meta-analysis were conducted on studies from accessible electronic databases. Each VNTR variant was examined in each gender independently by comparing with the pooled results of other alleles.ResultsA total of six independent case–control studies including 1022 SIDS cases and 1839 controls were enrolled in this meta-analysis. In both of the whole populations and Caucasian populations, male infants with the low-MAOA-expression alleles (2R+3R) were found to exhibit a statistically significant increased risk of SIDS, whereas those with a 4R allele exhibited a reduced risk of SIDS. Besides, an increased risk of SIDS was detected in male Caucasian infants with 2R or 3R alleles. However, none of the allele or genotype variants was associated with SIDS in female victims.ConclusionIn male Caucasian infants, the low expression of MAOA promoter VNTR alleles (2R and 3R) is associated with an increased risk of SIDS, and the existence of the 4R allele could be regarded as a protective factor.

Relationship Between Polymorphisms of Interleukin-1 Receptor Antagonist (IL-1Ra) Genes and Susceptibility to Systemic Lupus Erythematosus in Iranian Population.

Interleukin (IL)-1 has a major role in cell destruction and inflammation. IL-1 receptor antagonist (IL-1RN or IL-1Ra) is a natural anti-inflammatory molecule that blocks IL-1. We intended to determine whether IL-1RN or IL-1Ra variable number tandem repeat (VNTR) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE) in a series of patients in the Northeastern part of Iran. Genomic DNA was extracted from the whole blood of 104 SLE patients and 209 subjects without SLE as a control group. The control group was matched for age and gender with SLE patients. Then, genomic DNA was genotyped by polymerase chain reaction (PCR) method for a length polymorphism in intron 2 of the IL-1RN gene. Of five alleles, only allele 4 of IL-1RN had a higher frequency in healthy subjects (2.4%) compared to SLE patients (0), with a statistically significant difference (P= 0.03). Eleven kinds of polymorphisms of IL-1RN were found including 1/1, 1/2, 2/2, 3/3, 1/3, 3/5, 2/3, 2/5, 1/5, 4/4 and 1/4 in both groups. In genotype frequency, there was no statistically significant difference regarding gene polymorphism kinds between the two groups (P= 0.29). Alleles 4 of IL-1RN may have a protective role against SLE susceptibility. However, SLE was not associated with any of the 11 kinds of genotype IL1-RN gene polymorphisms studied here.

Interleukin 1 receptor antagonist gene variable number of tandem repeats polymorphism and cutaneous melanoma.

Immunity and cytokines serve crucial roles in cutaneous melanoma. The present study investigated whether a variable number tandem repeat (VNTR) polymorphism of interleukin-1 receptor antagonist (IL-1RA) gene (IL-1RN) located in intron 2 (rs2234663) is associated with cutaneous melanoma. A total of 515 subjects were studied, 133 of which were cutaneous melanoma cases (72 stage I+II non-metastatic melanoma cases and 61 stage III+IV metastatic melanoma cases), and 382 subjects were matching healthy controls from the Friuli-Venezia-Giulia Region located in Northeast Italy, an area with a high melanoma incidence. The IL-1RN-VNTR polymorphism was determined by DNA fragment length analysis following PCR amplification. According to the number of 86-bp repeats, five different IL-1RN alleles were identified: Allele 1 (4-repeats), allele 2 (2-repeats, short allele), allele 3 (5-repeats), allele 4 (3-repeats) and allele 5 (6-repeats). Alleles with three or more 86-bp repeats, i.e. allele 1, 3, 4 and 5 were collectively denoted as long (L) repeats. The present study revealed that IL-1RN-VNTR 1/2 and 2/L genotypes were more frequent among patients with cutaneous melanoma (43.6 and 45.1%, respectively) compared with healthy controls [29.6 and 30.6%, respectively; odds ratio (OR), 1.84; CI, 1.22–2.77; P=0.003; and OR, 1.66; CI, 1.24–2.79; P=0.002, respectively]. Conversely, the IL-1RN-VNTR 1/1 genotype was less frequent among melanoma cases (45.9%) compared with healthy controls (57.9%; OR, 0.62; CI, 0.41–0.92; P=0.017). Comparison of metastatic vs. non-metastatic melanoma cases identified no significant differences. The present study first demonstrated that carriage of the 1/1 IL-1RN-VNTR genotype was protective, whereas 1/2 and 2/L was a risk factor for patients with cutaneous melanoma vs. healthy controls. The short allele 2 was associated with higher expression levels of IL-1RA, a potent competitive inhibitor of the proinflammatory cytokines IL-1α and IL-1β. VNTR-IL-1RN polymorphism may affect susceptibility to melanoma and, thus, it is a potential novel diagnostic biomarker for melanoma. The present study increased the understanding of genetic melanoma susceptibility/carcinogenesis, and may indicate novel strategies in the personalized prevention of cutaneous melanoma.

MAOA-VNTR genotype affects structural and functional connectivity in distributed brain networks.

Previous studies have linked the low expression variant of a variable number of tandem repeat polymorphism in the monoamine oxidase A gene (MAOA‐L) to the risk for impulsivity and aggression, brain developmental abnormalities, altered cortico‐limbic circuit function, and an exaggerated neural serotonergic tone. However, the neurobiological effects of this variant on human brain network architecture are incompletely understood. We studied healthy individuals and used multimodal neuroimaging (sample size range: 219–284 across modalities) and network‐based statistics (NBS) to probe the specificity of MAOA‐L‐related connectomic alterations to cortical‐limbic circuits and the emotion processing domain. We assessed the spatial distribution of affected links across several neuroimaging tasks and data modalities to identify potential alterations in network architecture. Our results revealed a distributed network of node links with a significantly increased connectivity in MAOA‐L carriers compared to the carriers of the high expression (H) variant. The hyperconnectivity phenotype primarily consisted of between‐lobe (“anisocoupled”) network links and showed a pronounced involvement of frontal‐temporal connections. Hyperconnectivity was observed across functional magnetic resonance imaging (fMRI) of implicit emotion processing (p FWE = .037), resting‐state fMRI (p FWE = .022), and diffusion tensor imaging (p FWE = .044) data, while no effects were seen in fMRI data of another cognitive domain, that is, spatial working memory (p FWE = .540). These observations are in line with prior research on the MAOA‐L variant and complement these existing data by novel insights into the specificity and spatial distribution of the neurogenetic effects. Our work highlights the value of multimodal network connectomic approaches for imaging genetics.

Meta-analysis of the association of IL1-RN variable number of tandem repeats polymorphism with osteoarthritis risk

ObjectiveThe aim of this meta-analysis was to clarify the role of Interleukin-1 receptor antagonist gene (IL1-RN) Variable Number of Tandem Repeats (VNTR) polymorphism on the risk of OA by means of meta-analysis. MethodsEligible articles were retrieved from PubMed, Web of science and Google scholar with a total of 1187 OA cases and 2659 controls. The strength of the association between the IL1-RN VNTR polymorphism and the risk of OA was assessed by odds ratios (ORs) with the corresponding 95% confidence interval (CI) for each study. ResultsThe meta-analysis of seven published studies retrieved from the literature search showed a significantly increased OA risk in the recessive model analysis (22 vs 2L + LL: Pb = 0.18, I2 = 32.8, OR(95% CI) = 1.50(1.12, 2.02), P = 0.007), the additive model analysis (22 vs LL: Pb = 0.08, I2 = 46.8, OR(95% CI) = 1.56(1.15, 2.12), P = 0.004) and in the allele contrast model (2 vs L: Pb = 0.02, I2 = 58.8, OR(95% CI) = 1.20(1.05, 1.36), P = 0.007). By subgroup analysis, the IL1-RN VNTR polymorphism was found to be significantly associated with OA susceptibility in Caucasian and Hospital based case-control study (HCC) groups. ConclusionThis meta-analysis showed that IL1-RN VNTR polymorphism may increase the susceptibility to OA. More studies with detailed information are needed to validate our conclusion. Level of evidenceLevel III, diagnostic study.

PER3 gene regulation of sleep-wake behavior as a function of latitude

ObjectivesWe searched for interactions between PER3 gene VNTR polymorphism, latitude, sleep duration, diurnal sleepiness, and social jetlag. DesignWe selected samples from 3 distinct cities along the latitudinal range of Brazil and comprising the same time zone. SettingUndergraduate universities located in 3 major cities of Brazil. ParticipantsA total of 980 undergraduate students: 276 from Maceio (latitude 9°), 358 from Campinas (latitude 22°), and 346 from Porto Alegre (latitude 30°). MeasurementsPER3 variable number of tandem repeats genotyping, diurnal sleepiness, sleep duration (weekdays and weekend), chronotype, and social jetlag. ResultsLatitude is associated with a differential expression of circadian and sleep profiles. We observed a shift toward eveningness with increased latitude and increased social jetlag and diurnal sleepiness at latitude 30°. Moreover, our results suggest that the PER3 variable number of tandem repeats polymorphism has a modulatory effect on these circadian and sleep profiles: the variant PER34/4 is associated with a smaller difference in the sleep duration on weekdays among different latitudes and is associated with longer sleep duration on weekends just at latitude 30°, even when compared to both other genotypes at the same latitude. On the other hand, irrespective of the genotype, volunteers from latitude 30° expressed increased social jetlag and diurnal sleepiness. ConclusionsThe seasonal variation in the light/dark cycle, tied to latitude, together with the tight social time constraints that young adults are subjected to during weekdays, generates differences in the sleep phenotypes. Volunteers with the PER34/4 variant who live farther from the equator have a greater increase in their weekend sleep duration.

Impact of eNOS 27-bp VNTR (4b/a) gene polymorphism with the risk of Systemic Lupus Erythematosus in south Indian subjects

ObjectiveEndothelial nitric oxide synthase (eNOS) is constitutively expressed by vascular endothelium including glomerular endothelium. Functional polymorphisms, -786T>C (rs2070744) promoter variant, 27 bp VNTR (4b/a) in intron 4 and 894G>T (rs1799983) exon variant of eNOS are known to alter the eNOS expression and activity leading to altered NO levels and contribute to the development of vascular and renal disease risk. Thus it might have a role in SLE risk and development of glomerulonephritis. Hence, the present study is aimed to investigate the role of eNOS polymorphisms in South Indian SLE patients. MethodsFive hundred and four subjects (219 SLE cases and 285 controls) were included in the present case-control study. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for -786T>C and 894G>T SNPs. Another, 4a4b variable number of tandem repeat polymorphism was genotyped using direct PCR method using primer pairs flanking the 27 bp direct repeat region in intron 4 of eNOS gene. ResultsOur analysis revealed that intron 4 27 bp VNTR genotype frequency differ significantly between the SLE patients and controls (OR: 1.73, 95% CI %:1.18–2.54, P = 0.004). Further, “a allele” frequency was significantly higher in SLE patients as compared to the controls (20 vs. 13.8%) (OR: 1.56, 95%CI: 1.11–2.18, P = 0.01). However, promoter polymorphism −786T>C and missense variant 894G>T were not significantly different between the SLE cases and controls (OR: 0.92, 95%CI: 0.64–1.33, P = 0.7 and OR: 1.4, 95%CI: 0.95–2.06, P = 0.095 respectively). Furthermore, no association was found between any of the three polymorphisms with lupus nephritis phenotype. Increased plasma nitrate levels were observed in SLE patients (36.79 ± 2.83 μM/L) as compared to healthy controls (28.53 ± 1.94 μM/L) (P = 0.01). In addition, the genotype-based simulations have indicated that combined effect of eNOS polymorphisms contribute to 30.5% variability in NO production. ConclusionResults of the present study indicate that 27-bp VNTR polymorphism in intron 4 of eNOS gene polymorphism may be the significant risk factor for SLE in south Indian subjects.

DNA Methylation at the DAT Promoter and Risk for Psychopathology: Intergenerational Transmission between School-Age Youths and Their Parents in a Community Sample.

The effect of gene polymorphisms and promoter methylation, associated with maladaptive developmental outcomes, vary depending on environmental factors (e.g., parental psychopathology). Most studies have focused on 0- to 5-year-old children, adolescents, or adults, whereas there is dearth of research on school-age youths and pre-adolescents. In a sample of 21 families recruited at schools, we addressed parents' psychopathological symptoms (through SCL-90-R); offspring emotional-behavioral functioning (through CBCL-6-18); dopamine transporter gene (DAT1) for epigenetic status of the 5'-untranslated region (UTR) and for genotype, i.e., variable number of tandem repeats polymorphism at the 3'-UTR. Possible associations were explored between bio-genetic and psychological characteristics within the same individual and between triplets of children, mothers, and fathers. DAT methylation of CpG at positions M1, M6, and M7 in mothers was correlated with maternal (phobic) anxiety, whereas in fathers' position M6 was related to paternal depression, anxiety, hostility, psychoticism, and higher Global Severity Index (GSI). No significant correlations were found between maternal and offspring DAT methylation. Significant correlations were found between fathers' methylation at CpG M1 and children's methylation at CpG M6. Linear regressions showed that mothers and fathers' GSI predicted children's methylation at CpG sites M2, M3, and M6, whereas fathers' GSI predicted children's methylation at CpG sites, particularly M1, M2, and M6. Moreover, offspring methylation of DAT at CpG M2 predicted somatic complaint, internalizing and attention problems; methylation of DAT at CpG M6 predicted withdraw. This study may have important clinical implication for the prevention and treatment of emotional-behavioral difficulties in children, as it adds to previous knowledge about the role of genetic and environmental factors in predicting psychopathological symptoms within non-clinical populations.

Association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism with vitiligo susceptibility in Gujarat population.

Vitiligo is a multifactorial, polygenic, autoimmune skin disorder caused by selective destruction of melanocytes. Interleukin 1 receptor antagonist intron 2 polymorphism was found to be associated with various autoimmune disorders. We aimed to investigate the association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism (rs2234663) with vitiligo to assess interleukin 1 receptor antagonist transcript levels and to perform possible genotype-phenotype correlation. Three hundred and seven vitiligo patients and 316 controls were enrolled in the study, genotyping of interleukin 1 receptor antagonist rs2234663 was performed by polymerase chain reaction, and relative gene expression of interleukin 1 receptor antagonist was carried out in peripheral blood mononuclear cells from patients (n = 36) and controls (n = 36) by real-time-PCR. A significant difference was observed in the frequency of interleukin 1 receptor antagonist *A (1/2) genotype among patients with active and stable vitiligo (P = 0.0172). Interleukin 1 receptor antagonist*A (2/2) genotype and allele frequencies were significantly different between SV patients and controls (P = 0.0246 and P = 0.0046, respectively). Significant difference was also observed for interleukin 1 receptor antagonist*A2 (allele) in active and stable vitiligo patients (P = 0.0060). However, other comparisons did not show any significant difference in genotype and allele frequencies. Moreover, interleukin 1 receptor antagonist*A (3/2) genotype was observed only in patients whereas interleukin 1 receptor antagonist*A (5/2) was observed only in controls. Gene expression analysis showed no significant difference in interleukin 1 receptor antagonist transcript levels in patients compared to controls (P = 0.5962). Interestingly, genotype-phenotype correlation analysis revealed that individuals with IL1RN*A (2/2) exhibited higher interleukin 1 receptor antagonist expression compared to other major genotypes interleukin 1 receptor antagonist*A (1/2) (P = 0.01) and interleukin 1 receptor antagonist*A (1/1) (P = 0.03). More case-control studies on interleukin 1 receptor antagonist rs2234663 polymorphism and gene expression from different ethnic populations are required to explore the impact of interleukin 1 receptor antagonist in vitiligo susceptibility. Interleukin 1 receptor antagonist*A2 might be a risk factor for progressive vitiligo.

Divisive influence of interleukin-1 receptor antagonist polymorphisms in melanoma patients.

The interleukin-1 receptor antagonist (IL-1RA) contributes to tumor survival and progression in multiple cancer entities. IL-1RA polymorphisms influence IL-1RA expression patterns and function. A known polymorphism was correlated with clinical outcomes in melanoma patients with particularly aggressive disease. DNA of 343 controls and 97 melanoma patients with poor prognostic indicators (time from diagnosis to death, nodal status, metastasis) was analyzed for a variable number of tandem repeat polymorphisms (VNTR) of the IL-1RA gene. Five alleles containing two (allele 2), three (allele 4), four (allele 1), five (allele 3) or six (allele 5) 86-bp repeats were targeted via PCR amplification. Genotype 1/2 is less common in the melanoma patient group vs. the control (28.8% vs. 39.6%; p = 0.06). Significant was the stage of the melanoma in order to predict the survivability (p = 0.008). The 1/1 and 1/2 genotype appeared to have lower hazards ratios than the 2/2 genotype (p > 0.05). Compared to the general population, the distribution of alleles coding for IL-1RA is different in melanoma patients. This alteration and the potential impact on tumor protein function and systemic inflammatory response may warrant further investigation.

Interleukin-4 Gene Intron 3 VNTR Polymorphism in Type 2 Diabetes Patients with Peripheral Neuropathy

ABSTRACTObjective: Diabetic peripheral neuropathy (DPN) is one of late complications of diabetes mellitus. The aim of this study was to evaluate the association between variable number tandem repeat (VNTR) polymorphism in intron 3 of interleukin-4 gene and risk of DPN.Methods: We examined 926 T2DM patients and 420 healthy controls. In the patient group, 44% had DPN. Genomic DNA was isolated from all subjects and genotyped for the IL-4 VNTR polymorphism by polymerase chain reaction (PCR).Results: No significant difference was observed in the frequency of minor P1 allele between T2DM patients and controls (OR 1.00, 95% CI 0.81–1.23, p = 0.988). The distribution of IL-4 VNTR polymorphism was compared between patients with DPN and those without it. The polymorphism was not significantly associated with DPN in studied subjects. In comparison of 406 T2DM patients with DPN and 520 patients without it, the OR (95% CI) for P1 allele was 0.82 (0.65–1.04), p = 0.10 and for P1P1 genotype 1.00 (0.53–1.89), p = 0.991. When two subgroups of patients with DPN, those with cardiovascular disease (CVD) and without CVD, were compared, subgroup with coexisting CVD had significantly higher frequency of P1 allele than patients without CVD, with odds ratio for the P1 allele 3.27 (95% CI 1.83–5.83), p = 0.0001.Conclusion: Our results demonstrated that VNTR polymorphism in the IL-4 gene is associated with DPN in type 2 diabetes patients with coexisting CVD.

Association study of the polymorphism of MAOA gene with panic disorder

Objective To explore the association between monoamine oxidase A (MAOA) variable number tandem repeat (VNTR) polymorphism and panic disorder, and then to compare panic disorder(PD) severity patient with different MAOA VNTR genotypes. Methods The structured clinical interview for the diagnostic and statistical manual of mental disorders fourth edition (DSM-IV) Axis I Disorders (SCID-1) was administered by a trained clinical psychiatrist, 135 patients with PD and 195 healthy controls were recruited.MAOA-VNTR polymorphism were measured by fluorescent tags amplification product length polymorphism technology, Chi-square test was used to compare the distribution difference between each genotype and the allele frequency distribution. Results ①Whether male or female, there was no statistically significant difference between case group and healthy control group in the genotype and allele frequencies of MAOA-VNTR polymorphism (χ2=1.574, 1.894, 3.588; all P 0.05). ③However, there was significant difference between genotypes and panic disorder severity in the female with panic disorder((13.15±3.47), (16.57±4.34), (15.27±4.91); F=4.222, P<0.05). MAOA VNTR-L/L carriers experienced more serious panic (16.57±4.34) than the patient with MAOA VNTR-H/H (13.15±3.47)(P<0.01) by LSD multiple test. Conclusion No association between MAOA-VNTR polymorphism and panic disorder is found in Chinese Han population, but low activity homozygous genotype may be related to the severity of panic disorder in female patient with panic disorder. Key words: Panic disorder; Monoamine oxidase A gene; Polymorphism

The association between P selectin glycoprotein ligand 1 gene variable number of tandem repeats polymorphism and risk of thrombosis in Behçet's disease.

Behçet's disease (BD) has been recognized as an unclassified type of vasculitis with an accompanying tendency to thrombosis. No disease-specific pathology has been demonstrated so far to explain the prothrombotic state, and this predisposition is considered to be associated with endothelial activation/dysfunction. P-selectin glycoprotein ligand-1 (PSGL-1) variable number of tandem repeat (VNTR) polymorphism has an impact on the protein length, and heterozygosity affect of the PSGL-1 to P-selectin interaction, which has been found to be associated with an increased risk of thrombosis in patients with antiphospholipid syndrome. We aimed to analyze the association of PSGL-1 gene polymorphism, in a group of BD patients with and without thrombosis. The study group consisted of 136 BD patients (112 male, 24 female) with thrombosis, 120 BD patients without thrombosis (54 male, 66 female) during at least 5years disease course, and 190 healthy controls (103 male, 87 female) All patients fulfilled the International Study Group criteria for classification of BD. Genotyping for the PSGL-1 gene exon 2 VNTR polymorphism was carried out with the amplification of genomic DNA and running of the polymerase chain reaction product on agarose gel electrophoresis. The frequency of heterozygous genotypes (AB+AC+BC) was greater in BD patients with thrombosis compared to BD patients without thrombosis (33.1% vs. 20.8%, P=0.028, odds ratio=1.85). However, the increased frequency of heterozygous genotypes in BD patients with thrombosis did not reach a statistically significant level compared to healthy controls (33.1% vs. 32.6%). PSGL-1 VNTR polymorphism may have limited contribution to the thrombotic tendency in patients with BD.