Gene Variable Number Tandem Repeat Research Articles

The relationship between the aggrecan VNTR polymorphism and its content in lumbar intervertebral discs.

There is a specific polymorphism of the ACAN gene called the variable number of tandem repeats (VNTR), which is particularly interesting in the light of the development of intervertebral disc pathology and associated low back pain. The nucleus pulposus specimens were harvested from the L5/S1 intervertebral discs. The aggrecan content was determined using enzyme- linked immunosorbent assay (ELISA). Moreover, the VNTR polymorphism in the ACAN gene was evaluated. The genotyping of VNTR polymorphism in ACAN gene was successful in 94 tissue samples (48 homozygotes and 46 heterozygotes). The alleles were divided into four groups, in accordance with the number of tandem repeats in the ACAN gene. No difference between groups in the mean aggrecan mass nor in the mean degree of tissue moisture was observed. No relationship between the ACAN gene VNTR polymorphism and the aggrecan content was observed in studied Caucasian cadavers. Such a relationship may be a more complex phenomenon and exists in other populations.

Interplay between Serotonin, Immune Response, and Intestinal Dysbiosis in Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disorder characterized by periods of activity and remission. IBD includes Crohn's disease (CD) and ulcerative colitis (UC), and even though IBD has not been considered as a heritable disease, there are genetic variants associated with increased risk for the disease. 5-Hydroxytriptamine (5-HT), or serotonin, exerts a wide range of gastrointestinal effects under both normal and pathological conditions. Furthermore, Serotonin Transporter (SERT) coded by Solute Carrier Family 6 Member 4 (SLC6A4) gene (located in the 17q11.1-q12 chromosome), possesses genetic variants, such as Serotonin Transporter Gene Variable Number Tandem Repeat in Intron 2 (STin2-VNTR) and Serotonin-Transporter-linked promoter region (5-HTTLPR), which have an influence over the functionality of SERT in the re-uptake and bioavailability of serotonin. The intestinal microbiota is a crucial actor in normal human gut physiology, exerting effects on serotonin, SERT function, and inflammatory processes. As a consequence of abnormal serotonin signaling and SERT function under these inflammatory processes, the use of selective serotonin re-uptake inhibitors (SSRIs) has been seen to improve disease activity and extraintestinal manifestations, such as depression and anxiety. The aim of this study is to integrate scientific data linking the intestinal microbiota as a regulator of gut serotonin signaling and re-uptake, as well as its role in the pathogenesis of IBD. We performed a narrative review, including a literature search in the PubMed database of both review and original articles (no date restriction), as well as information about the SLC6A4 gene and its genetic variants obtained from the Ensembl website. Scientific evidence from in vitro, in vivo, and clinical trials regarding the use of selective serotonin reuptake inhibitors as an adjuvant therapy in patients with IBD is also discussed. A total of 194 articles were used between reviews, in vivo, in vitro studies, and clinical trials.

Helicobacter pylori virulent genes and host interleukin 1 are associated with demographic factors for an increased risk of gastritis

AimHelicobacter pylori is a predominant pathogen for the human race and causes gastrointestinal diseases as well as can be an increased risk for cancer. This study examined the bacterial and host genes involved in gastritis and the environmental influences to understand the disease outcome. MethodsPolymerase chain reaction assay was used to analyze the variations in virulence-associated genes of H. pylori in gastritis patients. Human interleukin 1 beta gene polymorphisms and IL-1 receptor antagonist gene (IL-1RN intron 2) variable number tandem repeats were evaluated by PCR and single-strand conformation polymorphism analysis, respectively. Various demographic factors were analyzed and all the statistical tests were two-sided. ResultsInfection with cagA, cagA – Asian lineage positive strains of H. pylori was associated with an increased risk for gastritis. IL-1B-511*T carriers homozygous for the short allele of IL-1RN (IL-1RN*2/*2) had an increased risk for gastritis for the cagA carrier. The odd ratio (OR – 0.17; 95% CI – 0.03 to 0.08; P = 0.04) was significant in certain bacterial (cagA) and host (IL-1RN*2) high-risk genotypes in the gastritis patients. ConclusionThe pathogen and the host genetics in relation to lifestyle habits provide a tool for defining the high-risk individuals and strategize H. pylori eradication programs.

Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer

The aim of this study is to evaluate the association of interleukin-4 (IL-4) gene intron 3 and interleukin-1 receptor antagonist (IL-1Ra) gene intron 2 variable number tandem repeat (VNTR) polymorphisms with bladder cancer (BC) susceptibility in Turkish population. A total of 75 BC patients and 126 healthy controls were included in this case-control study. Genotyping for the interested polymorphisms were analyzed through polymerase chain reaction (PCR). The strength of association between both IL-4 and IL-1Ra gene VNTRs and BC susceptibility was estimated utilizing odds ratio (OR) with corresponding 95% confidence interval (CI). In the study, no statistically significant differences were determined in the allele distributions for either in IL-4 gene intron 3 VNTR (OR= 1.33; CI 0.704-2,41, p=0.390) or in IL-1Ra gene intron 2 VNTR polymorphisms (OR= 0.890; CI 0.569-1.394, p=0.346) between BC patients and control groups. The genotype distributions of IL-4 gene were estimated for RP1/RP2 (OR= 1.55; CI 0.11-7.74, p = 0.590) and RP1/RP1 (OR= 2.08; CI 0.48-9.06, p = 0.320), found no difference between BC and control groups. The genotype distributions of IL-1Ra gene were estimated for 2L (OR= 1.401; CI 0.753-2.610, p = 0.287) and 22 (OR=0.908; CI 0.252-3.276, p = 0.883) and found no difference between BC and control groups. This study suggest that there were no statistically significant differences determined either in genotype or allele distributions between BC patients and control groups for both IL-4 intron 3 VNTR and IL-1Ra intron 2 VNTR polymorphisms in Turkish population and therefore there was no association of these variants with BC risk in this population.

A circadian rhythm gene (PER3) VNTR variant as possible risk factor in cohort of Turkish females with primary dysmenorrhea

Primary dysmenorrhea (PDM), which is the most prevalent problem related to the menstrual cycle in women of reproductive age, is due to sleep disorders and negative moods. Circadian rhythms, which are the immediate 24-h processes, enable an organism to adapt the suitable physiological responses to the environmental light-dark changes. Disturbed circadian rhythms are closely associated with several diseases, including sleep disorders. It has been reported that variable number tandem repeat (VNTR) variant in the coding region of circadian rhythm gene PERIOD 3 (PER3) affects sleep. Therefore, in the present study, we investigated the association between PDM and PER3 VNTR variant in Turkish females. A sample of 122 females with PDM and 150 healthy females were included in the study. Genoytyping of PER3 VNTR variant was performed on DNA by polymerase chain reaction (PCR) analysis using specific primers. We evaluated the relation between PER3 VNTR variant and PDM by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). In our analyses of genotype data collected from total 272 subjects, we found that the PER3 VNTR variant was associated with development of PDM [codominant model (5/5 vs. 4/4 + 4/5): OR = 0.664; 95% CI, 0.39–1.10; p = 0.05). The three genotypes of the VNTR variant (4/4, 4/5, and 5/5) and their allelic frequencies showed nonsignificant differences between patients and control group (p > 0.05). In summary, PER3 VNTR variant may be associated with PDM in a Turkish female. However, further studies in different ethnic populations are needed to address the full role of this variant in PDM.

Association between vitamin D receptor gene polymorphism (rs731236) and aggrecan gene VNTR polymorphism with the risk of lumbar intervertebral disc degeneration.

Background:Low back pain is one of the most common causes of referral to physicians. Lumbar disc degeneration (LDD) is the main cause of back pain in different countries. It seems that genetic factors are more effective than environmental factors in the developing of degenerative phenomena. The aim of this investigation, therefore, was to study the association of the aggrecan gene (ACAN) variable number tandem repeat (VNTR) and the vitamin D receptor (VDR) rs731236 (TaqI) polymorphisms, with lumbar intervertebral disc degeneration in a population in the North of Iran.Methods:In this study, 55 patients with symptomatic intervertebral disk degeneration and 55 control subjects were included. VDR gene polymorphism was genotyped by PCR-based RFLP. The isolated DNA was used to genotype the VNTR of ACAN gene via conventional PCR.Results:For VDR gene polymorphism, the CC genotype (OR=5.337, P=0.019) was significantly higher among the patients compared with the controls, revealing a higher frequency of the C allele in patients compared with controls (OR=2.707, P=0.005). The lower number of frequent repetitions in the VNTR aggrecan gene was associated with a six-time increase of lumbar disc degeneration. Also, high BMI can be considered as an independent factor in the incidence of this disease.Conclusion:Aggrecan gene VNTR polymorphism had an association with degeneration of lumbar intervertebral discs that the shorter VNTR repeats increasing the chance of the disc degeneration in this population in the North of Iran. Moreover, an association between the mutant allele (C) of VDR gene TaqI polymorphism and disc degeneration is found.

IL1RN VNTR Polymorphism and kidney damage in sickle cell anemia patients

Introduction: Sickle cell anemia (SCA) is a chronic illness associated with acute and chronic hemolytic anemia, recurrent vaso-occlusion episodes, intense pain, progressive multiple organ damage, and early mortality. Inflammation plays a significant role in the pathophysiology of SCA. Elevated levels of pro-inflammatory cytokines are involved in worsening the degree of kidney damage in SCA patients. Objectives: The present study aimed to assess whether IL1RN VNTR polymorphism is associated with kidney damage in patients with SCA. Patients and Methods: We have investigated 190 SCA patients (104 with Normal kidney function and 86 with kidney damage). Creatinine-based estimated glomerular filtration rate (eGFR) was calculated to assess kidney function. Interleukin-1 receptor antagonist gene (IL1RN) variable number tandem repeats (VNTR) genotypes were analyzed using PCR-electrophoresis. The association between IL1RN-VNTR and kidney damage was evaluated by using χ2 test. Odds ratios (OR) and 95% CI were calculated. The relationship between kidney damage and fetal hemoglobin (HbF) and their interaction with IL1RN-VNTR genotypes, was investigated using a Mantel-Haenszel (M-H) stratified analysis. Results: There were no significant differences in genotype frequencies between SCA patients with or without kidney damage (P=0.107). Furthermore, no significant interactions between IL1RN VNTR and HbF on determining kidney damage were found. Conclusion: These results conflict with the biological plausibility that interleukin levels modulate SCA pathophysiology and may deserve further exploration.

Possible Association of PER2/PER3 Variable Number Tandem Repeat Polymorphism Variants with Susceptibility and Clinical Characteristics in Pancreatic Cancer.

Objective: Pancreatic cancer (PC) is a serious disease with poor outcomes, and its prevalence has been increasing steadily. The circadian rhythm (CR) is involved in multiple physiological events and maintains homeostasis. Alterations in the CR elevate the risk of developing cancer. The present case-control research was carried out to estimate the possible association between PERIOD2/PERIOD3 (PER2/PER3) gene variable number tandem repeat polymorphism (VNTR) variants and PC in the Turkish population. Materials and Methods: A total of 198 subjects (78 patients with PC and 120 healthy controls) were enrolled in this work. Genomic DNA was collected from peripheral blood mononuclear cells, and genotypic analyses was performed using a polymerase chain reaction (PCR) method. Odds ratio (OR) with a 95% confidence interval (95% CI) was calculated using the χ2 test. Results: The frequency of the 4R (4 repeats)/3R (3 repeats), 3R/3R genotypes, and 3R allele of PER2 VNTR in patients with PC was significantly higher than in the control group (p = 0003, p = 0.00004, respectively). PER2 VNTR 4/5 genotype was related to perineural invasion (p = 0.040). The genotype and allele distribution of PER3 VNTR variant did not show any statistical difference between the two groups (p > 0.05). The PER2/PER3 VNTR 4/5-4R/3R combined genotype was increased in the patient group (p = 0.013), while 4/5-4R/4R combined genotype was increased in the control group (p = 0.0001). Conclusions: Our work has indicated that PER2 VNTR 3R allele may play a crucial role in the pathogenesis of PC in Turkish patients, which may become a useful marker for predicting the development of PC. Furthermore, the PER2 VNTR genotype seems to be related to perineural invasion in PC.

VNTR Variant of the eNOS Gene and its Relationship with Osteoporosis in Postmenopausal Turkish Women

Osteoporosis (OP) is the most common type of systemic bone disease characterized by low bone mass and micro-structure deterioration of bone tissue, with a consequent increase in bone fragility and fracture risk. Nitric oxide (NO), produced by the enzyme endothelial nitric oxide synthase (eNOS) in endothelial cells, has considerable effects on bone cell function. The objective of this case-control study was to investigate the potential association between the eNOS gene Variable Number Tandem Repeat (VNTR) variant and susceptibility of OP, in Turkish postmenopausal female patients. One hundred and fifty female patients and 100 age-matched healthy females were enrolled in the present study. The eNOS gene VNTR variant was genotyped with a polymerase chain reaction (PCR) method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. The mean age of the patients was 60.32±8.65 years. It was found that the eNOS VNTR variant genotype and allele frequencies were not significantly different between the patient and control groups (p>0.05).

Association of IL-1Ra and IL-4 Gene VNTRs with Susceptibility to Prostate Cancer in Turkish Population

Abstract—Prostate cancer (PCa) is a very common type of cancer among men. It was revealed that Interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1Ra) genes had important functions such as development of prostate cells or regulating the inflammatory processes. The important role of cytokines in inflammatory mechanisms leads to the possibility that polymorphisms of these genes may contribute to the formation of prostate cancer. In this study, we aimed to investigate the association of variable number tandem repeat (VNTR) polymorphisms in the IL-1Ra and IL-4 genes with PCa in Turkish population. 70 prostate cancer patients and 110 healthy controls were involved in a case-control study. Genotype distributions and allele frequencies for the IL-1Ra intron 2 (rs2234663) and IL-4 intron 3 (rs79071878) VNTR polymorphisms were analyzed by using PCR technique. No statistically significant association was identified for both IL-1Ra intron 2 and IL-4 intron 3 polymorphisms between PCa patients and controls (P > 0.05). IL-1Ra intron 2 and IL-4 intron-3 VNTR polymorphisms were not found to be risk factors in prostate cancer and its development in Turkish population.

Analysis of Interleukin-1 Receptor Antagonist Variable Number Tandem Repeat Variant in Recurrent Aphthous Stomatitis.

Recurrent aphthous stomatitis (RAS) is one of the common oral inflammatory diseases. As immunological and genetic factors have been held responsible for the pathogenesis of RAS, the objective of this study was to determine whether the interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) variant is a risk factor for the development of RAS in Turkish patients and to define its contribution to the increased risk. The IL-1Ra VNTR variant was evaluated in 169 RAS patients and 171 healthy controls by the polymerase chain reaction (PCR) method. No statistically significant difference was found in the genotype distributions and allele frequencies of IL-1Ra VNTR variant between RAS patients and healthy controls. Lack of association between IL-1Ra VNTR variant and RAS could indicate that IL-1Ra has no significant role in the pathophysiology of RAS. However, it still appears to be very worthwhile to continue to search for cytokine gene variants in order to predict the development of such disease.

Variants in the BACH2 and CLEC16A gene might be associated with susceptibility to insulin-triggered type1 diabetes.

Aim/IntroductionInsulin administration was found to trigger type 1 diabetes in six Japanese type 2 diabetes patients with type 1 diabetes high‐risk human leukocyte antigen class II and the class I allele of the insulin gene variable number tandem repeat genotype. The objective of the present study was to assess the contribution of non‐human leukocyte antigen single‐nucleotide polymorphisms (SNPs) to the risk of developing insulin‐triggered type 1 diabetes.Materials and MethodsWe genotyped 13 type 1 diabetes susceptible SNPs in six patients and compared them with those in Japanese controls (Hap Map3‐JPT). The SNPs that showed statistically significant results were further analyzed using non‐diabetic control participants and participants with type 2 diabetes at the Ehime University Hospital.ResultsThe risk allele frequency of BACH2 rs3757247 in the six patients was significantly more frequent than that in 86 Japanese controls (P = 0.038). No significant difference in the allele frequency was observed in the other SNPs. This result was confirmed by the findings that the risk allele frequency of BACH2 in the six patients was significantly higher than that in the non‐diabetic control participants (n = 179) and type 2 diabetes with or without insulin treatment (n = 154 or n = 152; P = 0.035, 0.034 or 0.037, respectively). Despite being statistically not significant, the six patients were all homozygous for the CLEC16A rs12708716 risk allele and five were homozygous for the CLEC16A rs2903692 risk allele.ConclusionsIn addition to type 1 diabetes high‐risk human leukocyte antigen class II and the class I allele of the insulin gene variable number tandem repeat genotype, the possibility that the risk variants of BACH2 and CLEC16A could contribute to the development of insulin‐triggered type 1 diabetes cannot be excluded.

A systematic review of the relationship between the distributions of aggrecan gene VNTR polymorphism and degenerative disc disease/osteoarthritis.

ObjectivesDegenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA.MethodsThis study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.ResultsThe final selection of seven studies was comprehensively evaluated and includes results for 2928 alleles. The most frequent allele among all the studies was allele 27. After comparing the distributions of each allele with others, statistically significant differences have been found in the distribution of the alleles by the two groups, with an over-representation of allele (A)21 (disease: 3.22%, control: 0.44%). Thus, carrying A21 increased the risk of DDD. Such an association was not found to be statistically significant when considering the risk of OA.ConclusionsThe findings suggest that VNTR A21 seems to be associated with higher risk to DDD, however, such an association may not be statistically significant regarding the risk of OA.Cite this article: L. Cong, G. Tu, D. Liang. A systematic review of the relationship between the distributions of aggrecan gene VNTR polymorphism and degenerative disc disease/osteoarthritis. Bone Joint Res 2018;7:308–317. DOI: 10.1302/2046-3758.74.BJR-2017-0207.R1

Association of Interleukin-1 Gene cluster polymorphisms with coronary slow flow phenomenon.

Objective:Coronary slow flow phenomenon (CSFP) is characterized by the decreased rate of contrast progression in epicardial coronary arte-ries in the absence of significant coronary stenosis. Mounting evidence has showed a significant association between inflammation and CSFP severity. This study aimed to evaluate possible associations between interleukin-1 receptor antagonist (IL-1ra) gene variable number tandem repeat (VNTR), IL-1β -511 single nucleotide (SNP), and IL-1β+3954 SNP mutations with CSFP.Methods:Forty-eight patients with CSFP and 62 controls with angiographically normal coronary arteries were prospectively enrolled in the study. Genotypes were assessed using the polymerase chain reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP) technique.Results:Homozygote genotype for allele 2 of+3954 C>T 2/2 genotype was significantly more frequent in patients with CSFP than in the control group, whereas 1/2 genotype was more frequent in the control group (35.4% versus 14.5% for 2/2 genotype and 25% versus 35.5% for 1/2 genotype in CSFP and control groups, respectively, X2=6.6; p=0.04). The allelic frequency of allele 2 of this polymorphism was significantly higher in the CSFP group than in the control group (47.9% versus 28.6% in the control group, X2=5.6; p=0.02). However, there was no significant difference with regard to genotype or allelic frequencies of IL-1ra VNTR or IL-1β -511 SNP polymorphisms between patients with CSFP and controls.Conclusion:IL-1β+3954 SNP mutations are significantly more common in patients with CSFP. It may suggest that the tendency for inflammation may contribute to the presence of this phenomenon.

The IL-1Ra gene variable number tandem repeat variant is associated with susceptibility to temporomandibular disorders in Turkish population.

Temporomandibular joint disorders (TMD) are a group of disorders involving temporomandibular joint and related structures. Interleukine-1 receptor antagonist (IL-1Ra) is an important anti-inflammatory molecule that competes with other interleukin-1 molecules. This study was designed to investigate the possible association of the IL-1Ra VNTR variant with the risk of TMD in the Turkish population. Peripheral blood samples were collected from 100 patients with TMD (23 males, 77 females) and 110 healthy individuals (35 males, 75 females). Genotyping of IL-1Ra 86bp VNTR variant was evaluated by gel electrophoresis after polymerase chain reaction (PCR). Our results show that there is a statistically significant difference between TMD patients and control group with respect to IL-1Ra genotype distribution and allele frequencies. 1.2, 1.4, and 4.4 genotypes were more common in patients, while 2.2 and 3.3 genotypes were rarer (P<.000). Frequency of alleles 1 and 4 was higher in patient groups (P<.000), whereas alleles 2 and 3 had a lower frequency in patients with TMD (P<.000). This is the first correlation study that evaluates the association between IL-1Ra gene VNTR variant and TMD. The VNTR variant related to IL-1Ra gene showed a strong pattern of association with TMD that may have a potential impact on disease counseling and management. Larger studies with various ethnicities are needed to establish the impact of IL-1Ra VNTR variant on risk of developing TMD.

CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study.

We investigated the association between an aggrecan gene (ACAN) polymorphism and lumbar disc herniation (LDH). This was a case-control study with quinquennial age and gender groups. The study comprised 119 men and women aged between 20 and 60 from Goiânia (Brazil). Of these, 39 were allocated to the case group (Ca) and 80 to the control group (Ct). We gathered sociodemographic and clinical data, and peripheral blood samples. DNA was isolated for genotyping the ACAN variable number tandem repeat (VNTR) via conventional polymerase chain reaction (PCR). Data were statistically analyzed using the chi-square test, multiple comparison analysis, the Student t-test, and odds ratios, with a level of significance set at 5% (P ≤ 0.05). The groups were homogenous in terms of sociodemographic, anthropometric, and life style variables. The allele score for the ACAN VNTR was significantly lower in volunteers with LDH; the A22 allele was significantly more prevalent in this same group; the Ca group presented greater frequency of short alleles A13-A25, whereas the Ct group presented a higher frequency of long alleles. However, this difference was not statistically significant. In both groups, the most common alleles were A28, A27, and A29, and the A26/A26 genotype was significantly more common in the Ca group. The results showed an association between short alleles and LDH among the investigated adults (Ca), corroborating the hypothesis that aggrecan with shorter repeat lengths can lead to a reduction in the physiological proteoglycan function of intervertebral disc hydration and, consequently, increased individual susceptibility to LDH.

GENETIC ASPECTS OF PANNICULITIS IN A RUSSIAN POPULATION: A PILOT STUDY

Numerous clinical observations show that the human genetic background plays an important role in predisposition to many diseases. Objective: to investigate a possible relationship of the polymorphisms in 19 A/G leptin (LEP) gene, in the interleukin (IL)-1 receptor antagonist (IL-1RA) gene VNTR (variable number of tandem repeats), and in the -174G/C IL-6 gene to the risk of developing the clinical phenotypes of panniculitis (PN), clinical and laboratory parameters. Subjects and methods. The study enrolled 54 patients (48 women and 6 men) aged 15 to 76 years with a documented diagnosis of PN who had been treated at the V.A. Nasonova Research Institute of Rheumatology. Group 1 of 46 patients with erythema nodosum (EN) and Group 2 of 8 with Weber-Christian panniculitis (WCP) were formed for genetic study. The genotyping data on 197 healthy unrelated individuals were used as a control. Clinical and laboratory information was available from 39 patients for genotyping 19A/G LEP gene polymorphism, that from 43 patients for -174G/C IL-6 gene polymorphism, and that from 46 patients for IL-1RA polymorphism. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) analysis. Results and discussion. The frequencies of the LEP 19 GG genotype and the LEP G allele in patients with EN and WCP were significantly higher than those in the controls (48.7 and 18.2%, p = 0.0004; 50.0 and 18.2%, p = 0.053; and 70.5 and 45.4%, p = 0.0002, respectively). The frequencies of the A1A1 genotype and A1 allele of IL-1RA gene VNTR polymorphism in EN group were significantly higher than those in the controls (67.4 and 44.2%, p=0.011; 80.4 and 61.6%, p = 0.002, respectively). The frequency of IL-6 -174GC polymorphism was also higher in the EN group than that in the controls (58.1 and 34.7%, p = 0.008). The -174G/C polymorphism showed a significant association with the site of erythema (p = 0.028). In patients with a single lesion of erythema on the body, the frequency of the -174 GC genotype was significantly higher than that in those with multiple foci of erythema (72.0 and 31.2%, respectively; p = 0.025). In the WCP group, analysis of variance showed an association of IL-1RA gene VNTR polymorphism with the intensity of pain, assessed by the visual analogue scale. The carriers of the A1A1 genotype had more severe pain than those of the A1A2 genotype (83.3±11.5 and 20.0±18.2 mm, respectively; p = 0.008). Conclusion. The findings suggest that genetic testing can be used to predict the clinical course of PN.

Insulin gene VNTR polymorphisms -2221MspI and -23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis.

A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive. We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls. For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of -23HphI on LADA. Our results support the existence of associations of INS with T1D and LADA.

The association of variable number of tandem repeats polymorphism in the endothelial nitric oxide synthase gene and diabetic retinopathy

To investigate the association between the variable number of tandem repeats (VNTR) polymorphism 4a/b in the endothelial nitric oxide synthase (eNOS) gene and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. cross-sectional study. A total of 278 type 2 diabetes patients were recruited, of whom 130 had DR, and 148 had diabetes without retinopathy (DWR). Of the 130 patients with DR, 34 had proliferative DR (PDR) and 96 had non-proliferative DR (NPDR). A number of 223 volunteers without diabetes from the same area were recruited as the control group. PCR and agarose gel electrophoresis methods were adopted to determine the 4a/b polymorphism genotypes of the eNOS gene. Statistical analysis was performed using the R statistical analysis package. Genotype distribution was compared using the χ(2) test. Numerical data were examined by Student t test. Genotypes and allele frequencies between cases and controls were compared using the χ(2) test or Fisher's exact test. Odd ratios (OR) and 95% confidence intervals (CI) were calculated according to the Woolf's equation. The frequencies of minor alleles (a) were 10.8% and 11.5% in the DR and DWR group, respectively. There were no statistical differences between the two groups (χ(2) = 0.07, P = 0.789). Also there were no statistical differences (χ(2) = 0.88; P = 0.643) in the distributions of the genotypes between DR group (bb 78.5%, ab 21.5%, aa 0.0%) and DWR group (bb 77.7%, ab 21.6%, aa 0.7%). Statistical differences were found in the frequencies of alleles, and the distributions of genotypes between diabetes group and the control group (χ(2) = 8.75, 10.39, P = 0.003, 0.006). However, after adjustment for age, blood pressure, cholesterol concentration, blood-fat and so on, it became insignificant (χ(2) = 0.97, 1.25, P = 3.224, 0.812). In the multiple regressions model including clinic factors such as the age of onset of diabetes, urinary albumin, insulin using, creatinine, glycated hemoglobin and fast glucose, no evidence showed that eNOS gene VNTR 4a/b was associated with diabetic retinopathy (OR = 0.37, 95% CI: 0.15-0.95). There was no significant association between eNOS gene VNTR 4a/b polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.

Association of the FAM46A gene VNTRs and BAG6 rs3117582 SNP with non small cell lung cancer (NSCLC) in Croatian and Norwegian populations.

We analyzed for associations between a variable number of tandem repeat (VNTR) polymorphism in the Family with sequence similarity 46, member A (FAM46A) gene and a single nucleotide polymorphism (rs3117582) in the BCL2-Associated Athanogene 6 (BAG6) with non small cell lung cancer in Croatian and Norwegian subjects. A total of 503 (262 Croatian and 241Norwegian) non small cell lung cancer patients and 897 controls (568 Croatian and 329 Norwegian) were analyzed. We found that the frequency of allele b (three VNTR repeats) of FAM46A gene was significantly increased in the patients compared to the healthy controls in the Croatian and the combined Croatian and Norwegian subjects. Genotype frequencies of cd (four and five VNTR repeats) and cc (four VNTR repeats homozygote) of the FAM46A gene were significantly decreased in the patients compared to the healthy controls in the Croatian and Norwegian subjects, respectively. Logistic regression analyses revealed FAM46A genotype cc to be an independent predictive factor for non small cell lung cancer risk in the Norwegian subjects after adjustment for age, gender and smoking status. This is the first study to suggest an association between the FAM46A gene VNTR polymorphisms and non small cell lung cancer. We found also that BAG6 rs3117582 SNP was associated with non small cell lung cancer in the Norwegian subjects and the combined Croatian-Norwegian subjects corroborating the earlier finding that BAG6 rs3117582 SNP was associated with lung cancer in Europeans. Logistic regression analyses revealed that genotypes and alleles of BAG6 were independent predictive factor for non small cell lung cancer risk in the Norwegian and combined Croatian-Norwegian subjects, after adjustment for age and gender.