Metformin and long non-coding RNAs in breast cancer.

Breast cancer (BC) is the second most common cancer and cause of death in women. In recent years many studies investigated the association of long non-coding RNAs (lncRNAs), as novel genetic factors, on BC risk, survival, clinical and pathological features. Recent studies also investigated the roles of metformin treatment as the firstline treatment for type 2 diabetes (T2D) played in lncRNAs expression/regulation or BC incidence, outcome, mortality and survival, separately. This comprehensive study aimed to review lncRNAs associated with BC features and identify metformin-regulated lncRNAs and their mechanisms of action on BC or other types of cancers. Finally, metformin affects BC by regulating five BC-associated lncRNAs including GAS5, HOTAIR, MALAT1, and H19, by several molecular mechanisms have been described in this review. In addition, metformin action on other types of cancers by regulating ten lncRNAs including AC006160.1, Loc100506691, lncRNA-AF085935, SNHG7, HULC, UCA1, H19, MALAT1, AFAP1-AS1, AC026904.1 is described.

Haplotypic variants of COVID-19 related genes are associated with blood pressure and metabolites levels.

The genetic association of coronavirus disease 2019 (COVID-19) with its complications has not been fully understood. This study aimed to identify variants and haplotypes of candidate genes implicated in COVID-19 related traits by combining the literature review and pathway analysis. To explore such genes, the protein-protein interactions and relevant pathways of COVID-19-associated genes were assessed. A number of variants on candidate genes were identified from Genome-wide association studies (GWASs) which were associated with COVID-19 related traits (p ˂ 10-6 ). Haplotypic blocks were assessed using haplotypic structures among the 1000 Genomes Project (r2 ≥ 0.8, D' ≥ 0.8). Further functional analyses were performed on the selected variants. The results demonstrated that a group of variants in ACE and AGT genes were significantly correlated with COVID-19 related traits. Three haplotypes were identified to be involved in the blood metabolites levels and the development of blood pressure. Functional analyses revealed that most GWAS index variants were expression quantitative trait loci and had transcription factor binding sites, exonic splicing enhancers or silencer activities. Furthermore, the proxy haplotype variants, rs4316, rs4353, rs4359, and three variants, namely rs2493133, rs2478543, and rs5051, were associated with blood metabolite and systolic blood pressure, respectively. These variants exerted more regulatory effects compared with other GWAS variants. The present study indicates that the genetic variants and candidate haplotypes of COVID-19 related genes are associated with blood pressure and blood metabolites. However, further observational studies are warranted to confirm these results.

Association of ACE gene polymorphisms with in-stent restenosis by stent type (biomime, supraflex, xience).

INTRODUCTION: Angiotensin Converting Enzyme or ACE is an exo-peptidase that causes the conversion of angiotensin I to angiotensin II, vasoconstriction, and aldosterone production. ACE gene polymorphism (I/D) affects enzyme activity and the risk of coronary artery disease or CAD. AIMS: To examine the role of ACE (I/D) Gene Polymorphisms by Stent Types (Biomime, Supraflex, Xience) the Ace gene allele and genotype frequencies were determined in patients who underwent angioplasty. MATERIAL & METHODS: Patients with in-stent restenosis (ISR+) (N = 53) and patients as non-ISR group (ISR-) (N = 68) have been enrolled in this study based on follow-up angiography > 1 year after PCI. Frequencies of allele and genotypes of the ACE (I/D) variant were determined using polymerase chain reaction (PCR). RESULTS: The genotypes and allele frequencies were not significantly different between the studied populations (p-Values > 0.05). However, there was a significant difference between people with a history of Clopidogrel use in the ISR- and ISR + groups observed (p-Values > 0.005). CONCLUSION: In the present study, there was no statistically significant relationship between ACE (I/D) gene polymorphism and the incidence of restenosis in patients who underwent repeat angiography. The results showed that the number of patients who received Clopidogrel in the ISR + group was significantly less than the ISR- group. This issue can indicate the inhibitory effect of Clopidogrel in the recurrence of stenosis.

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

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

Role of genetic polymorphisms in recurrent aphthous stomatitis: A systematic review and meta-analysis.

Recurrent aphthous stomatitis (RAS) is one of the most common oral ulcerative diseases with unknown etiology. Identifying the genetic markers can improve medical care and prevention of RAS. Genetics variants inflammatory agents are associated with the risk of RAS. Thus, this meta-analysis aimed to investigate the genetic polymorphisms in RAS. Electronic literature search was carried out on Scopus, PubMed, and Web of Science (WOS). The references of relevant reviews were also manually checked. The observational studies till the end of 2020 were included. Odds ratio (OR) was estimated by fixed and random effect model. Seventeen polymorphisms in 23 studies were included in analysis. Pooled analysis performed for 12 polymorphisms (IL-2+166, IL-2-330, IL-4-590, IL-4 RA1902, IL-6-597, TNF-α-308, NLRP3(rs4612666, rs10754558), MMP2- rs2285053, MMP9- rs11697325, MMP9- rs3918242, MMP9- rs17576, IL-1a-889, IL-10-819, and IL-12+1188). The meta-analyses carried out for six polymorphisms (IL-1ß-511, IL-1ß+3954, IL-6-174, IL-10-592, IL-10-1082, and serotonin transporter). There were following significant results for IL-10, 819 in allelic:1.46(1.04-2.05) and homozygote: 1.61(1.08-2.39) models, serotonin Transporter in allelic:0.53(0.40-0.71), recessive:0.56(0.35-0.90), dominant:0.35(0.22-0.57) and homozygote:0.30(0.17-0.54) models. IL-1ß-511 in dominant 0.69(0.50-0.95) and overdominant 0.73(0.55-0.96) models, IL-1ß+3954 in allelic 1.25(1.05-1.50), homozygote 1.67(1.05-2.63) and dominant 1.26(1.01-1.57) models, IL-6-174 in dominant 2.24(1.36-3.67), IL-10-592 in homozygote 0.41(0.23-0.72) and dominant 0.55(0.33-0.93), IL-10-1082 in allelic 1.19(1.01-1.39) and dominant 1.29(1.02-1.64). In conclusion, serotonin transporter(L/S), IL-10-819(T/C), IL-10-592(C/A), IL-10-1082(G/A), IL-1ß-511(C/T), IL-6-174(G/C), and IL-1ß+3954 (T/C) polymorphisms are associated with susceptibility to RAS. These variants could be potential predictors of RAS and could be used for the developing clinically effective genetic panel for RAS.

The importance of regulatory pathway mediated by Circ0001955 in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC. METHODS: After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed. RESULTS: Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters. CONCLUSION: Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.

The vitamin D receptor gene variants, ApaI, TaqI, BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress.

INTRODUCTION: To date, numerous disorders have been linked to vitamin D deficiency. Several lines of evidence indicate a relationship between vitamin D deficiency and the risk of developing type 2 diabetes. It has been postulated that vitamin D may influence insulin activity, which can predispose individuals to develop type 2 diabetes. MATERIALS AND METHODS: In this case-control study, 262 patients with definite type 2 diabetes were enrolled, considering whether they were being affected by diabetic foot ulcers or not. The plasma levels of vitamin D and homocysteine were measured using ELISA, and the PCR-RFLP technique was utilized to determine allele and genotype frequencies. The antioxidant capacity of plasma samples of diabetic patients was analyzed using the thiobarbituric acid reactive substance (TBARS) and ferric reducing ability of plasma (FRAP) assays. RESULTS: The obtained results demonstrated no significant difference in the frequency of TaqI and BsmI polymorphisms between the case and control groups. However, the frequency of genotypes and alleles of the ApaI polymorphism in the VDR gene significantly differed between the case and control groups. A significant correlation was found between ApaI polymorphism and oxidative stress, as patients with the GG genotype had lower levels of TBARS than those with other genotypes. Furthermore, in the case group, patients with the CC genotype of BsmI showed a significant decrease in TBARS levels. DISCUSSION: It seems that the plasma levels of vitamin D do not differ between patients with or without diabetic foot ulcers; however, the presence of some VDR gene polymorphisms is thought to be involved in the development of diabetic foot ulcers via increasing oxidative stress.

Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6.

Amyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The main purpose of this study was the induction of localized insulin-generated amyloidosis and the observation of silymarin effects on this process. In order to obtain amyloid structures, regular insulin was incubated at 37 °C for 24 h. Congo red absorbance and transmission electron microscopy images validated the formation of amyloid fibrils. Those fibrils were then injected subcutaneously into rats once per day for 6, 12 or 18 consecutive days in the presence or absence of silymarin, and caused development of firm waxy masses. These masses were excised and stained with Hematoxylin and Eosin, Congo red and Thioflavin S. Histological examination showed adipose cells and connective tissue in which amyloid deposition was visible. Amyloids decreased in the presence of silymarin, and the same effect was observed when silymarin was added to normal insulin and injected subsequently. Furthermore, plasma concentrations of MMP2, TNF-α, and IL-6 inflammatory factors were measured, and their gene expression was locally assessed in the masses by immunohistochemistry. All three factors increased in the amyloidosis state, while silymarin had an attenuating effect on their plasma levels and gene expression. In conclusion, we believe that silymarin could be effective in counteracting insulin-generated local amyloidosis.

ADA gene haplotype is associated with coronary-in-stent-restenosis.

BACKGROUND: Cardiovascular diseases (CVDs) are the most common and the first cause of death worldwide. While some studies have investigated the association of the Adenosine Deaminase (ADA) gene with CDVs, its roles on in-stent restenosis (ISR) has not been studied. METHODS AND RESULTS: In this study, we investigated the role of ADA gene variants in both genetic and haplotype models on the risk of ISR. 91 samples were included in this study. The subjects were divided into two groups regarding having or not-having ISR (n = 40 ISR+ and n = 51 ISR-). The genotyping for G22A (rs73598374) and A4223C (rs452159) polymorphisms was performed using PCR-RFLP method. Statistical analysis was performed by SPSS v. 20 and Haploview 4.2 softwares. The basic demographic conditions in ISR groups were statistically similar. There was a significant association between A allele of rs452159 ISR groups after adjustment (allelic model: P value = 0.028, OR(95%CI) = 0.366(0.149-0.899)), while rs73598374 polymorphism shows no significant association with ISR. In haplotype analysis, the GA (G:rs73598374/A:rs452159) haplotype decreased the risk of ISR (P value = 00.025, OR(95%CI) = 0.382(0.161-0.907)). CONCLUSIONS: This study suggests that A allele of ADA rs452159 polymorphism and GA (G:rs73598374/A:rs452159) haplotype may be related to decreased risk of ISR in CAD patients receiving drug-eluting stent and offers more observational studies on ADA variants in other populations to generate a potential haplotype panel for ISR risk assessment.

Investigation of TGF-ß1 gene variant and expression in a group of Iranian women with endometriosis.

PURPOSE: Endometriosis is defined as a common gynecologic and inflammatory disease. Transforming growth factor-beta 1 (TGF-ß1) gene and its protein level might play a role in the pathogenesis of endometriosis. The present study aimed for the first time to assess the associations between endometriosis risk and - 509 C/T (rs1800469) variant of the TGF-ß1 gene as well as TGF-ß1 mRNA expression in eutopic endometrium tissue of patients with and without endometriosis among a group of Iranian women. METHODS: Genotyping was carried out in 100 endometriosis patients (cases) with confirmed histological diagnosis of endometriosis and 197 non-endometriosis subjects (controls). The expression level of TGF-ß1 mRNA was determined using Real-Time PCR assay in 15 eutopic endometrium tissue of women with endometriosis and 15 healthy controls. RESULTS: There was a significant association for allele and genotype frequencies of rs1800469 variant and endometriosis. No significant difference for TGF-ß1 expression was observed between eutopic endometrium of patients and healthy group. Also, evaluation of TGF-ß1expression across the menstrual cycle showed the same level of TGF-ß1 among case and control subjects. CONCLUSION: Our investigations indicated enough evidence for the effect of TGF-ß1 genetic variant on endometriosis risk in an Iranian population. Furthermore, we could not find any relations between TGF-ß1 mRNA expression and susceptibility to endometriosis.

The Effect of Metformin on Expression of Long Non-coding RNA H19 in Endometrial Cancer.

Background: Endometrial cancer is the fourth most widespread cancer among females, with a growing prevalence in recent years. Management by combined therapies along with surgery, radiotherapy, and chemotherapy have improved patients' prognoses. Besides, the development of new therapies helps preserve fertility and prognosis in aggressive tumors. The purpose of this research was to identify the efficacy of metformin on the H19 long non-coding RNA expression in endometrial cancer to provide further insight into the pathogenesis and treatment of the disease. Methods: A total of 23 patients with endometrial cancer, diagnosed by biopsy or diagnostic curettage, were recruited and divided into three groups, before and after metformin treatment and placebo. Real-time PCR was used to evaluate the H19 expression in cancer tissue in all patients. Results: : It has been observed that in endometrial tissue of the "after-metformin" treatment group, the H19 expression level was significantly reduced, compared with the "before-metformin" treatment group, but not in comparison with the placebo. These findings indicate that metformin reduced the H19 expression in endometrial cancer. Conclusion: Anti-diabetic drugs, such as metformin, may be beneficial by reducing the H19 expression in endometrial cancer due to the H19 relation to cancer progression.

Association of MTHFR C677T polymorphism with elevated homocysteine level and disease development in vitiligo.

Increasing evidence on the association of MTHFR gene polymorphism and serum homocysteine levels with autoimmune diseases such as vitiligo has made the MTHFR gene a very interesting candidate to be evaluated in different ethnicities and populations. We aimed to evaluate the levels of serum homocysteine and vitamin B12 and their associations with MTHFR C677T polymorphism in the Iranian population. This case-control study included 104 patients with vitiligo and 100 age- and sex-matched healthy control subjects. Serum vitamin B12 and homocysteine levels were measured by a chemiluminescence assay. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used for genotyping the polymorphism. The mean serum homocysteine levels were significantly higher in cases than controls and associated with disease activity (p < .001). Furthermore, the homozygous MTHFR C677T variant genotype was associated with vitiligo development (adjusted OR: 3.52, 95% CI: 1.09-11.32, p = .02) and elevated homocysteine level (p < .001). There was no association between serum vitamin B12 levels and the MTHFR C677T genotype. The homozygous variant MTHFR C677T may be considered as a risk factor for both elevated homocysteine levels and the development of vitiligo in the Iranian population. Although these results are not conclusive, they could elucidate the contribution of genetic and immune-mediated inflammatory factors to the pathogenesis of vitiligo.

Association of microRNA gene polymorphisms with Type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder with growing prevalence and increasing economic burden. Based on the role of genetics and epigenetic factors on T2DM, we aimed to carry a systematic review and meta-analysis for all miRNA gene polymorphisms and risk of T2DM. MATERIALS AND METHODS: A computerized literature search was carried out on PubMed, Web of Science, Scopus, Embase, as well as references of relevant review/meta-analysis. Key search terms were "Diabetes Mellitus, Type 2," "MicroRNAs," and "Polymorphism, Single Nucleotide." All types of observational studies from January 1, 1992, to November 30, 2019, were included, without language restriction. Data analysis was performed using R programming language (3.5.2). Level of heterogeneity was obtained by Cochran's Q test (P < 0.05), and subgroup analysis was performed based on ethnicity. RESULTS: Thirty-two polymorphisms from fifteen articles were included. Meta-analysis was carried out based on minor allele frequencies. Seven studies with 2193 cases and 3963 controls were included for rs2910164 polymorphism. In subgroup analysis, there were significant results in Caucasian population in dominant model (odds ratio [OR] =1.12; 95% confidence interval [CI]: 0.83-1.51), homozygote model (OR = 1.78; 95% CI: 1.06-3.00), heterozygote model (OR = 1.77; 95% CI: 1.03-3.05), and recessive model (OR = 1.78; 95% CI: 1.07-2.96). Four studies with 2085 cases and 1933 controls were included for rs895819 polymorphism. Overall, there was no significant result for association with rs895819, but subgroup analysis revealed that minor allele significantly decreased the risk of T2DM in Caucasians by recessive model (OR = 0.34; 95% CI: 0.18-0.66), dominant model (OR = 0.70; 95% CI: 0.52-0.94), homozygote model (OR = 0.32; 95% CI: 0.16-0.62), heterozygote model (OR = 0.37; 95% CI: 0.19-0.74), allelic model (OR = 0.67; 95% CI: 0.52-0.85). CONCLUSION: The minor allele of rs2910164 may increase the risk of T2DM by leading to lower level of miR-146a. In contrast, minor allele of rs895819 may decrease the risk of T2DM by leading to higher level of miR-27a.

Integrative analyses of triple negative dysregulated transcripts compared with non-triple negative tumors and their functional and molecular interactions.

Triple-negative (TN) tumors are a subtype of breast cancer with aggressive behaviors and limited targeted therapies. Microarray studies were not concerned with interactions and functional relations of dysregulated transcripts. Here, we aimed to conduct integrative strategy to analyze gene and miRNA available microarray data as well as bioinformatic analyses to catch a more inclusive picture of pivotal dysregulated transcripts and their interactions in TN tumors. Several online datasets and offline bioinformatic tools were used to detect differentially expressed (DE) transcripts, both protein and nonprotein coding, in TN compared with non-TN tumors and their functional and molecular interactions. Sixteen upregulated and 58 downregulated genes with a log fold change higher or equal to | 2 | were identified, including nine transcription factors. Coexpression network revealed EN1 as a hub gene, moreover Kaplan-Meier plotter survival analysis indicated that it was an appropriate prognostic marker for TN patients with breast cancer. Functional annotation analysis of protein-protein interaction network showed FOXM1 as an upexpressed and ESR1 as a downexpressed hub genes are suitable targets as far as antitumor protein therapy is concerned in TN breast cancers. The consensus analysis of two microRNA datasets revealed seven DE miRNAs. The gene-transcriptional factor (TF)-miRNA network revealed mir-135b and mir-29b are the hub nodes and involved in feedback loops with GATA3. This study suggests that dysregulated TFs and miRNAs have pivotal roles in regulation of TN oncotranscriptomic profile and might become both biomarkers and therapeutic targets.

Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer.

Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood. In the recent years, the newly discovered mechanism in the RNA world is "competing endogenous RNA (ceRNA)" which proposes regulatory dialogues between different RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). In the latest BC research, various studies have revealed that dysregulation of several ceRNA networks (ceRNETs) between these ncRNAs has fundamental roles in establishing the hallmarks of BC development. And it is thought that such a discovery could open a new window for a better understanding of the hidden aspects of breast tumors. Besides, it probably can provide new biomarkers and potential efficient therapeutic targets for BC. This review will discuss the existing body of knowledge regarding the key functions of ceRNETs and then highlights the emerging roles of some recently discovered ceRNETs in several hallmarks of BC. Moreover, we propose for the first time the "ceRnome" as a new term in the present article for RNA research.

Autoimmune Polyglandular Syndrome Type 1: a case report.

BACKGROUND: Mutations of the autoimmune regulator gene (AIRE), located on chromosome 21q22.3, are recognized as the cause of a rare monogenic organ-specific autoimmune disorder called autoimmune polyglandular syndrome type 1 (APS-1). Three major components of this syndrome include chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenocortical failure. CASE PRESENTATION: We report a 19-year-old girl, who was born in an Iranian Muslim family with a clinical diagnosis of APS-1. To identify the causative mutation, a direct sequencing of the entire AIRE gene sequence was performed by Sanger sequencing method. Three distinct variants were discovered, including c.1095 + 2 T > A, c.1197 T > C (rs1800521) and c.1578 T > C (rs1133779), in intron 9, exons 10 and 14 of the AIRE gene, respectively. CONCLUSIONS: To the best of our knowledge, this is the first report of an Iranian Muslim APS-1 patient with combination of these variations. In addition, the effect of c.1095 + 2 T > A mutation on AIRE mRNA expression was reported for the first time. This study expands the diversity of variants that could cause APS-1. More genetic studies are required to determine the exact frequency of these variants and their diagnostic significance.

Association of interleukin-6 polymorphisms with obesity: A systematic review and meta-analysis.

Obesity is a common metabolic disorder with increasing trend all around the world. Owing to the role of pro-inflammatory cytokines on obesity, we aimed to investigate the role of interleukin-6 (IL-6) polymorphisms on risk of obesity. Electronic literatures were searched in Web of Science, PubMed, Embase, and Scopus. The references of relevant reviews and included studies were also manually checked. All types of observational studies from 1 January 1992 to 28 February 2018 were included. Odds ratio (OR) was estimated by fixed and random effect model. Subgroup analysis was carried out based on age statues. Pooling analysis of eligible studies have been considered for rs2069845 and rs1800796, and no significant results were observed. Minor allele of IL-6 rs1800797polymorphism decreased the risk of obesity/overweight in allelic 0.74 (0.59-0.92), dominant 0.65 (0.49-0.85), and over-dominant 0.66 (0.51-0.87) models. Fourteen eligible studies were included for rs1800795. According to BMI, C allele showed increased risk of obesity in genetic models containing homozygote model 1.47 (1.02-2.12) for body mass index (BMI) ≥ 25 vs. BMI < 25, recessive model 1.32 (1.07-1.63) for BMI ≥ 30 vs. BMI < 25, and homozygote model 1.35 (1.10-1.66) for BMI ≥ 30 vs. BMI < 30. In overall definition of obesity more significant results were observed, including homozygote model in obese vs. normal 1.71 (1.14-2.56). Similarly, subgroups analysis revealed additional significant results. Minor alleles of rs1800795 raised and rs1800797 reduced the risk of obesity, while rs1800796 and rs2069845 may not be associated. However, more observational studies are recommended to confirm these results.

The Association between Genetic Variation in Wnt Transcription Factor TCF7L2 (TCF4) and Alopecia Areata.

Background: Alopecia areata (AA) is a non-scarring hair loss with a polymorphous presentation ranging from patchy lesions to involvement of the entire scalp. The disease is the consequence of an autoimmune attack on hair bulbs that results in a premature transition of hair follicles to catagen and telogen. Thus the Wnt/ß-catenin signaling pathway that regulates the hair cycling might be involved in the pathogenesis of AA. Genetic variations in the components of Wnt/ß-catenin could greatly alter their adaptive mechanisms against an immunologic attack. Objectives: Our aim was to investigate the association between AA and genetic polymorphisms in the TCF7L2 gene, one of the most important components of the Wnt/ß-catenin pathway. Methods: This is a case-control study of 145 patients with AA and 152 healthy controls. Genotyping of the TCF7L2 gene (rs7903146) was performed via the ARMS-PCR method (amplification refractory mutation system- polymerase chain reaction). The allele and genotype distribution was compared between the two groups. Results: The frequency of the T allele (0.38 vs. 0.28, odds ratio = 1.56, 95% CI = 1.09-2.17, p = 0.013) and TT + CT genotypes (0.68 vs. 0.53, odds ratio = 1.88, 95% CI = 1.17-3.02, p = 0.008) were significantly higher in AA patients. Conclusions: This study indicates that the TCF7L2 gene variant is associated with AA. Its contribution to disease pathogenesis could either be through a hair cycling defect or dendritic cell dysregulation.

Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case-control study.

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) - 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the - 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that - 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis.

Is the +405 G/C single nucleotide polymorphism of the vascular endothelial growth factor (VEGF) gene associated with late-onset vitiligo?

The increasing body of evidence for the relationship between the vascular endothelial growth factor (VEGF) polymorphism and autoimmune disorders combined with the enhanced expression of this angiogenic factor in vitiligo makes VEGF a very interesting candidate gene to be investigated in vitiligo. The aim of this study was to evaluate the possible associations between the +405 G/C single nucleotide polymorphisms (SNP) of the VEGF gene (rs2010963) and vitiligo. The independent case-control population sample of 152 patients with vitiligo and 152 matched controls was evaluated in this study. A questionnaire was completed for each vitiligo patient to document the demographic and clinical characteristics of the patients. All enrolled individuals had a venous blood sample collected. Genotype frequencies for +405 G/C VEGF gene polymorphism were determined using polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) analysis. There were no significant differences in genotype or allele distributions for this SNP between cases and controls. However, we observed a significant association between GG genotype and higher age at onset of vitiligo (p = 0.04). Moreover, patients stratification revealed a significant increase in the frequency of GG genotype compared to CC + CG genotypes in patients with the late onset (≥20 years) vitiligo (p = 0.05). Although these results are not conclusive, they could potentially lead to considering the angiogenic factors as a potential target for therapy in late-onset vitiligo.