Variable Number Of Tandem Repeats Polymorphism Research Articles

Effects of Work Stress and Period3 Gene Polymorphism and Their Interaction on Sleep Quality of Non-Manual Workers in Xinjiang, China: A Cross-Sectional Study.

Work stress has been found to be associated with sleep quality in various occupational groups, and genetic factors such as variable number tandem repeat polymorphism in the Period3 (Per3) gene also influence the circadian sleep-wake process. Therefore, the present study aimed to evaluate the sleep quality status of non-manual workers in Xinjiang, China and to analyse the effects of work stress and Per3 gene polymorphism and their interaction on sleep quality. A cluster sampling method was used to randomly select 1700 non-manual workers in Urumqi, Xinjiang. The work stress and sleep quality of these workers were evaluated using the Effort–Reward Imbalance Inventory (ERI) and the Pittsburgh Sleep Quality Index (PSQI). Next, 20% of the questionnaire respondents were randomly selected for genetic polymorphism analysis. The polymerase chain reaction-restriction fragment length polymorphism technique was used to determine Per3 gene polymorphism. The detection rate of sleep quality problems differed between the different work stress groups (p < 0.05), suggesting that non-manual workers with high levels of work stress are more likely to have sleep quality problems. Regression analysis revealed that the Per3 gene (OR = 3.315, 95% CI: 1.672–6.574) was the influencing factor for poor sleep quality after adjusting for confounding factors, such as occupation, length of service, education, and monthly income. Interaction analysis showed that Per34/5,5/5 × high work stress (OR = 2.511, 95% CI: 1.635–3.855) had a higher risk of developing sleep quality problems as compared to Per34/4 × low work stress after adjusting for confounding factors. The structural equation modelling showed no mediating effect between work stress and Per3 gene polymorphism. The results of this study show that both work stress and Per3 gene polymorphism independently affect sleep quality of nonmanual workers from Xinjiang, and the interaction between these two factors may increase the risk of sleep quality problems. Therefore, to improve sleep quality, individuals with genetic susceptibility should avoid or reduce as much as possible self-stimulation by work-related exposures such as high levels of external work stress.

Frequency of CYP2C9 Promoter Variable Number Tandem Repeat Polymorphism in a Spanish Population: Linkage Disequilibrium with CYP2C9*3 Allele.

Background: A promoter variable number tandem repeat polymorphism (pVNTR) of CYP2C9 is described with three types of fragments: short (pVNTR-S), medium (pVNTR-M) and long (pVNTR-L). The pVNTR-S allele reduces the CYP2C9 mRNA level in the human liver, and it was found to be in high linkage disequilibrium (LD) with the CYP2C9*3 allele in a White American population. The aim of the present study is to determine the presence and frequency of CYP2C9 pVNTR in a Spanish population, as well as analyzing whether the pVNTR-S allele is in LD with the CYP2C9*3 allele in this population. Subjects and Methods: A total of 209 subjects from Spain participated in the study. The CYP2C9 promoter region was amplified and analyzed using capillary electrophoresis. Genotyping for CYP2C9*2 and *3 variants was performed using a fluorescence-based allele-specific TaqMan allelic discrimination assay. Results: The frequencies of CYP2C9 pVNTR-L, M and S variant alleles are 0.10, 0.82 and 0.08, respectively. A high LD between CYP2C9 pVNTR-S and CYP2C9*3 variant alleles is observed (D’ = 0.929, r2 = 0.884). Conclusion: The results from the present study show that both CYP2C9 pVNTR and CYP2C9*3 are in a high LD, which could help to better understand the lower metabolic activity exhibited by CYP2C9*3 allele carriers. These data might be relevant for implementation in the diverse clinical guidelines for the pharmacogenetic analysis of the CYP2C9 gene before treatment with different drugs, such as non-steroidal anti-inflammatory drugs, warfarin, phenytoin and statins.

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.

Significant Association of Variable Number Tandem Repeat Polymorphism rs58335419 in the MIR137 Gene With the Risk of Gastric and Colon Cancers.

The purpose of the article: The MIR137 gene acts as a tumor-suppressor gene in colon and gastric cancers. The aim of this study was to investigate the association of functional variable number tandem repeat (VNTR) polymorphism rs58335419 locating in the upstream of the MIR137 gene with the risk of colon and gastric cancers. Materials and methods: Totally, 429 individuals were contributed in the study, including 154 colon and 120 gastric cancer patients and 155 healthy controls. The target VNTR was genotyped using PCR and electrophoresis for all samples. Statistical analysis was performed using SPSS 21.0 software and by T, χ2 and logistic regression tests. Results: Excluding the rare genotypes, our results showed that genotype 3/5 (95% CI = 1.08–3.73, OR = 2.01, p = 0.026) significantly increased the risk of colon cancer but not gastric cancer (95% CI = 0.88–3.30, OR = 1.70, p = 0.114). Also, in the stratification analysis for VNTRs and sex, genotypes 3/4 (95% CI = 1.00–6.07, OR = 2.46, p = 0.049) and 3/5 (95% CI = 1.25–7.18, OR = 2.99, p = 0.014) significantly increased the risk of colon cancer in men but not in women. In addition, all genotypes including the rare genotypes as a group, significantly increase the risk of gastric (95% CI = 1.14–3.00, OR = 1.85, p = 0.012) and colon (95% CI = 1.38–3.43, OR = 2.17, p = 0.001) cancers compared to the genotype 3/3 as a reference. Conclusion: The results show that increasing the copy of VNTR in the MIR137 gene, increases the risk of colon and gastric cancers and can serve as a marker for susceptibility to colon and gastric cancers.

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.

VNTR polymorphism in the SLC6A3 gene does not influence dopamine transporter availability measured by [18F]FE-PE2I PET or [123I]FP-Cit SPECT.

To investigate the potential impact of polymorphism in the 3'-untranslated region (3'UTR) of the SLC6A3 gene (DAT1) on normal variation in dopamine transporter (DAT) imaging with [18F]FE-PE2I PET and [123I]FP-Cit SPECT. Thirty-six individuals (mean age 70.4±5.4 years) with normal [18F]FE-PE2I PET and [123I]FP-Cit SPECT were genotyped for variable number of tandem repeats (VNTR) in the 3'UTR of the DAT1 gene. The DAT-availability in the caudate and putamen as measured with [18F]FE-PE2I PET and [123I]FP-Cit SPECT, as well as in the substantia nigra with [18F]FE-PE2I PET were compared between the participants carrying one or two 9-repeat alleles (i.e. 9R+10R or 9R+9R; 47%) and the participants without a 9R allele (i.e. 10R+10R or 10R+11R; 53%). Nonparametric tests, linear regression analysis and mixed model analysis were used to assess any statistical difference in measured DAT availability between the two allele groups. The measured DAT-availability in PET- and SPECT-imaging tended to be slightly higher in the 9R-group; however, the difference did not reach statistical significance in either the caudate or the putamen or the substantia nigra. Instead, age did have a significant effect on the DAT level (P < 0.05) notwithstanding the genotype. No significant effect of DAT1-genotype was detectable in imaging with [18F]FE-PE2I PET or [123I]FP-Cit, instead, age accounted for the normal variation in DAT-PET and DAT-SPECT.

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation

Diş Laboratuvarı Teknisyenlerinde IL-1Ra ve IL-4 Geni VNTR Polimorfizmlerinin Analizi: Genotip-Fenotip Çalışması

For people working in dental prosthesis laboratories (DPL), metal alloys and methylmethacrylate-based monomers and polymers used in the laboratory can pose occupational risks. These risks can cause occupational health problems and toxic effects on human health. This study purposes of researching the effects of occupational exposure because of dental prosthesis manufacturing operations on variable number tandem repeat (VNTR) polymorphisms in IL-1Ra and IL-4 genes. 29 DPL workers, the experimental group, were given a questionnaire, including the symptoms that might arise due to occupational exposure, and their responses were compared with 30 participants as a control group. Genotype distributions and allele frequencies for IL-1Ra intron 2 (rs2234663) and IL-4 intron 3 (rs79071878) VNTR polymorphisms were analyzed using the PCR technique. Both IL-1Ra intron 2 and IL-4 intron 3 polymorphisms identified from the experimental and control groups were not statistically significantly different (p &amp;gt;.05). However, runny nose, burning throat, dyspnea and dryness and rash on the skin were significantly different when DPL workers were compared with the control group according to logistic regression analysis (p &amp;lt;.05). No statistical difference was found in other phenotypic characters. However, due to the limited sample size, our results need to be confirmed in large-scale studies.

The influence of IL1RN VNTR polymorphism on HPV infection among some tribal communities.

Persistent infection of human Papillomavirus is the main etiological factor for cervical cancer. Austro-Asiatic tribes are early settlers in India and they have unique genetic variations compared to other people. The immunological response is crucial for the prevention of viral associated diseases. Interleukin-1 receptor antagonist (IL-1RN) is considered being an important regulator of host immune surveillance. A total of 45 Santali tribal women and 10 Kora tribal women were enrolled in the present study and demographic variables were recorded during collection. Genomic DNA was extracted from cervical/vaginal swab samples. IL1RN variable number of tandem repeats (VNTR) polymorphisms and HPV types were determined by PCR-based assay. Association between IL1RN VNTR polymorphisms with the HPV infections among the tribal communities was determined by logistic regression analysis. HPV18 prevalence was significantly higher among tribal women. We observed that the polymorphism A2*A2 (p = 0.022; odds ratio [OR] (95% confidence interval [CI]) = 0.16 (0.03-0.86)] were more resistant to oncogenic HPV infection. Use of oral contraceptives was associated with higher relative risk (p = 0.008; OR [95% CI] = 5.39 [1.47-19.8]) for oncogenic HPV18 positivity among the tribal women. The A2 allele homozygosity of IL1RN VNTR was identified to be associated with the protection from oncogenic HPV infection among various tribal communities of West Bengal and therefore may be a useful marker of host immune response among them.

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.

A multicenter case\u2013control study of the effect of e-nos VNTR polymorphism on upper gastrointestinal hemorrhage in NSAID users

Bleeding in non-steroidal anti-inflammatory drug (NSAID) users limited their prescription. This first multicenter full case–control study (325 cases and 744 controls), explored the association of e-NOS intron 4 variable number tandem repeat (VNTR) polymorphism with upper gastrointestinal hemorrhage (UGIH) in NSAID exposed and unexposed populations and assessed any interaction between this polymorphism and NSAIDs. NSAID users carrying e-NOS intron 4 wild type genotype or VNTR polymorphism have higher odds of UGIH than those unexposed to NSAIDs [Odds Ratio (OR): 6.62 (95% Confidence Interval (CI): 4.24, 10.36) and OR: 5.41 (95% CI 2.62, 11.51), respectively], with no effect modification from VNTR polymorphism-NSAIDs interaction [Relative Excess Risk due to Interaction (RERI): −1.35 (95% CI −5.73, 3.03); Synergism Index (S): 0.77 (95% CI 0.31, 1.94)]. Similar findings were obtained for aspirin exposure. Non-aspirin NSAID users who carry e-NOS intron 4 VNTR polymorphism have lower odds of UGIH [OR: 4.02 (95% CI 1.85, 8.75) than those users with wild type genotype [OR: 6.52 (95% CI 4.09, 10.38)]; though the interaction estimates are not statistically significant [RERI: −2.68 (95% CI −6.67, 1.31); S: 0.53 (95% CI 0.18, 1.55)]. This exploratory study suggests that the odds of UGIH in NSAID or aspirin users does not modify according to patient´s e-NOS intron 4 genotype.

D1S111 and 33.4 Polymorphism as a Tool of Genetic Identity among Egyptians

Abstract Background The variable number tandem repeats (VNTR) are highly polymorphic markers. Due to their high polymorphic content, VNTR constitute useful tools in population genetic studies in understanding population and ethnic migrations throughout history. They also constitute preferred systems for DNA “fingerprinting”, criminal and forensic examinations and paternity testing, evaluating hematopoietic chimerism and in determining the origin of leukemic cells in patients with recurrent disease after BMT. Aim of the Work To standardize PCR protocols of 2 VNTR loci (D1S111/33.6 and 33.4) in order to detect allelic polymorphism among Egyptians as a tool in following up the chimeric status after allogenic stem cell transplantation. Patients and Methods The current study was conducted at Clinical Pathology Department of Ain Shams University Hospital between January 2018 and December 2019, a total of 130 subjects [65 pairs (allogenic stem cell transplantation donors and their recipients)] were included. D1S111/33.6 and 33.4 VNTR loci were evaluated in every subject by PCR technique to study their relative distribution and number of informative alleles detected in order to be used in chimerism follow up and population studies. Results Five alleles were found at D1S111/33.6 in 130 subjects with molecular weight ranging from 364 to 993 bp, frequency of homozygous alleles were 30.8% and it was 69.2% for heterozygous, 90 out of the total 130 subjects were heterozygous for 33.6, that means that the heterozygosity index for D1S111/33.6 is 69.2%, from the 65 pairs tested 31 pair were informative or discriminative with discriminative power 47.69%. For 33.4 we tried many PCR programs but no bands were detected at all. Conclusion D1S111/33.6 VNTR polymorphism is a dependable cost effective method in following up of allogenic stem cell transplantation recipients.

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

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

Thymidylate synthase locus LOH in combination with genotype has prognostic and predictive significance in colorectal cancer.

The aim of the current study was to investigate the prognostic and predictive significance of polymorphisms in the thymidylate synthase (TS) gene, alongside the loss of heterozygocity (LOH) at this gene locus in patients with colorectal cancer. Genotyping was carried out for a variable number tandem repeat (VNTR) polymorphism in the TS 5'-untranslated region, a G/C single nucleotide polymorphism (SNP) located within this VNTR, and for TS LOH status in 246 colorectal cancer and paired normal DNA samples. The results were analyzed in relation to clinicopathological features, including the prognostic and predictive significance of TS genotype in patients who underwent curative surgery. Complete VNTR, SNP and LOH information for TS was obtained in 226 cases. No significant associations were observed between normal tissue TS genotype status and clinicopathological features. LOH of TS was observed in 58% of tumor samples and was associated with poor prognosis independently of clinical stage. Cases exhibiting TS LOH were classified into the three groups of 2R/loss, 3G/loss and 3C/loss. Patients with 3C/loss genotype status had poor outcomes when treated by surgery alone, but their survival was similar to patients with other genotypes following Fluorouracil (5-FU)-based adjuvant chemotherapy. The results suggested that LOH of the TS locus may be a significant prognostic factor in colorectal cancer, with the genotype of the residual allele also demonstrating an influence on prognosis. In conclusion, LOH status should be considered when TS genotype is explored as a potential prognostic and predictive marker for 5-FU-based adjuvant chemotherapy in colorectal cancer.

Analysis of MNS16A VNTR polymorphic sequence variations of the TERT gene and associated risk for development of bladder cancer.

Background:The MNS16A variable number tandem repeat (VNTR) polymorphism of the human telomerase reverse transcriptase (hTERT) gene acts as a regulator of hTERT promoter activity and has been shown to have a role in the predisposition toward various cancers. The current study aimed to investigate the association between MNS16A VNTR alleles and genetic predisposition to bladder cancer in the Kashmir region of northern India.Materials and methods:A total of 130 patients with bladder cancer and 170 age- and gender-matched healthy controls were included in this study. Primer-specific polymerase chain reaction was used to genotype the different variants of VNTR alleles of the MNS16A VNTR polymorphism.Results:Short allele VNTR-243 (SS) genotype frequency significantly differed between cases (9.23%) and controls (3.52%) (OR = 3.08 [95% CI = 1.10–8.61], p = 0.042). The VNTR-243 short allele (S) was found significantly more frequent in bladder cancer cases (28.46%) than controls (20.88%) (OR = 1.50 [95% CI = 1.03–2.19], p = 0.034). Likewise, the long allele (LL) hTERT MNS16A genotype was distributed more frequently in low stage disease versus high stage disease (60.29% vs. 39.70%) (OR = 0.79 [95% CI = 0.39–1.60], p = 0.595).Conclusion:The MNS16A VNTR short allele (S) was associated with a higher risk for bladder cancer in our population as compared to long alleles.

Interleukin-1 Receptor Antagonist (IL-1RN) Gene Variable Number Tandem Repeats (VNTR) Polymorphism Association in men Infertility in Erbil City /Kurdistan Iraq

The interleukin-1 family has multifaceted roles in men٫s reproductive syste. Out of these is interleukin-1 receptor antagonist (IL-1RN) which exists in men gonads, and in case of infection and inflammatory process, its activity is increased. The current study aims to verify a possible linkage of Variable Number Tandem Repeat (VNTR) polymorphism of the IL-1RN gene with human men infertility. The study groups enrolled included 100 infertile men and 100 fertile and healthy men. Their seminal fluids were subjected to analysis. Also peripheral blood samples were collected for the assessment or detection of polymorphic Variable Number Tandem Repeats (VNTR) polymorphism of interleukin-1 receptor antagonist gene (IL-1RN). Two alleles, namely IL-1RN1 allele corresponding to 410bp fragment and IL-11RN2 that corresponding to 240bp fragments, are a marker for human men infertility, detected by PCR technique. The results delineated a high frequency of IL-1RN2 allelic gene variants (26%), and two VNTR allelic gene variants carriers IL-1RN1 and IL-1RN2 (16%) among infertile men with significant impacts on sperm motility and morphology (P&lt; 0.000-0.002) respectively. This prospective study inKurdistan region (Erbil –Iraq) defined a significant impact of VNTR polymorphism of IL-1RN gene in the etiology of men infertility especially on sperm motility and morphology; particularly carriers of IL-1RN2 allelic variants

Genetic association of interleukin-4 VNTR polymorphism with susceptibility to rheumatoid arthritis in South Gujarat population

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease, which causes swelling and severe pain within joints. The variable number tandem repeats (VNTR) polymorphism of interleukin-4 (IL4) gene has been associated with autoimmune diseases including RA. The study investigated the association of IL4 VNTR (IVS3; R1 > R2) polymorphism with RA susceptibility in South Gujarat population of India. Polymerase chain reaction (PCR) method was used for genotyping of IL4 VNTR polymorphism in 302 RA patients and 334 controls and ELISA was used for estimation of plasma IL-4 levels. The genotype and allele frequencies of the polymorphism were significantly differed between RA patients and control population (p < 0.0001), suggesting that IL4 VNTR polymorphism is associated with RA susceptibility in South Gujarat population. The susceptible ‘R2’ allele was prevalent in RA group as compared to the control group (79.4% vs 64.00%; p < 0.0001). Moreover, both the genotype and allele frequencies were significantly differed between severe and mild RA patients (p = 0.0039 & p = 0.0005 respectively). The plasma IL-4 levels (p = 0.0216) and genotype-phenotype correlation revealed significant increased IL-4 levels for R2R2 genotype in RA patients compared to controls (p = 0.0265). The IL-4 levels were significantly higher in R2R2 genotype when compared to R1R1 and R1R2 genotypes in RA patients (p = 0.007 & p = 0.03 respectively). Furthermore, IL-4 levels were significantly increased in severe RA patients compared to mild (p = 0.0293). Both, IL-4 levels and R2R2 genotypes were positively correlated with rheumatoid factor (r = 0.49, p = 0.0009 & r = 0.41, p = 0.035 respectively). Overall, the study for the first time suggests that IL4 VNTR R2 allele may be associated with susceptibility to RA in South Gujarat population and it is likely to play a role in increased IL-4 levels thereby contributing to RA pathogenesis.

Interleukin-1β and Interleukin-1 receptor antagonist gene polymorphism in pediatric patients with Helicobacter pylori-associated chronic gastritis.

The severity of Helicobacter pylori infection is determined by the interplay between bacterial virulence, host genetic and environmental factors. This study aimed to identify interleukin-1 beta (IL-1β) and interleukin receptor antagonist (IL-1RN) gene polymorphisms and their associations with H. pylori infection, and severity of chronic gastritis in Egyptian children. A case control study was conducted on 100 children (50 H. pylori positive and 50 controls). Genotyping of IL-1β-31 gene was done by PCR-CTPP (confronting two-pair primers), of IL-1β-511 was performed using allele specific PCR, and investigation of the variable number tandem repeat polymorphism of the IL-1RN gene was done by PCR. The genotype C/T of IL1β-511 was the predominant genotype (36/50; 72%) among H. pylori positive cases (p ≤ 0.001). The presence of C/T genotype at position 511 of IL1β was associated with increased risk of infection with H. pylori (p ≤ 0.001, odds ratio = 6.612) and with more severe disease (p = 0.004, odds ratio = 8.333). No association of IL-1β-31 or IL-1RN gene polymorphisms with H. pylori infection or with risk of severe gastric diseases was found. Children who carry two polymorphisms are almost four times at risk for development of H. pylori infection (p = 0.026, odds ratio = 3.937). Polymorphism at position -511 of IL1β gene is associated with increased risk of H. pylori infection as well as of severe corpus gastric disease in Egyptian children. This population should be considered a high-risk group, which needs regular gastric endoscopic surveillance, and should be target for H. pylori eradication. Lay summaryThe genotype C/T of IL1β-511 gene was the predominant genotype (36/50; 72%) among H. pylori positive children. Polymorphism at position -511 of IL1β gene is associated with increased risk of Helicobacter pylori infection as well as of severe corpus gastric disease in Egyptian children. No association of IL-1β-31 or IL-1RN gene polymorphisms with H. pylori infection or with risk of severe gastric diseases in Egyptian children.

Association of occupational stress, period circadian regulator 3 (PER3) gene polymorphism and their interaction with poor sleep quality.

Occupational stress is associated with sleep quality among workers and the human variable number tandem repeat (VNTR) polymorphism of the period circadian regulator 3 (PER3) gene relates to sleep-wake regulation. The main aims of the present study were to examine the effects of PER3 VNTR genotypes, occupational stress, and their interactions on sleep quality. A cross-sectional study was conducted and 729 workers were recruited in Sichuan. Sleep quality were assessed using the Pittsburgh Sleep Quality Index. Occupational stress was measured using the Generic Job Stress Questionnaire. PER3 genotypes were determined with polymerase chain reaction. High and medium occupational stress were linked to a higher risk of poor sleep quality than low levels. Unconditional logistic regression indicated that PER3 genotype was significantly associated with sleep quality, and an increased risk of poor sleep of >1.5-times was observed in those with the allele 5 compared to allele 4. The 5/5 genotype was associated with both sleep latency and sleep duration. Crossover analysis showed an occupational stress×PER3 interaction. Compared to subjects with both low and medium occupational stress and 4/4+4/5 genotype, those with both high occupational stress and 5/5 genotype had a higher risk of poor sleep quality. Stratified logistic analyses found that compared with low and medium occupational stress, high occupational stress increased the risk of poor sleep by more than five-times in 5/5 genotype carriers. Occupational stress and PER3 genotype had both separate and combined effects on poor sleep quality of workers. The results suggest that occupational stress may increase the risk of poor sleep quality through interaction with the PER3 gene polymorphism.