TCF7L2 Rs7903146 Polymorphism Research Articles

TCF7L2, CASC8, and GREM1 polymorphism and colorectal cancer in south-eastern Romanian population.

Colorectal cancer (CRC) is a heterogeneous disease with an increasing trend and with multiple epigenetic alterations and different molecular features, a major cause of mortality and morbidity. The Wnt/β-Catenin pathway is involved in multiple aspects of cell dynamics, architecture of developing gastrointestinal tissues, and intestinal tissue homeostasis in adults, but its aberrant activity plays an important role in every aspect of colorectal carcinogenesis. The aim of our study was to investigate the association of the TCF7L2 rs7903146, CASC8 rs6983267, and Gremlin1 (GREM1) rs16969681 polymorphism in patients with CRC without other pathologies. A case-control study conducted on 31 patients diagnosed with CRC and 30 healthy controls age and sex-matched with the patients. Real time PCR was used to determine the genotypes of rs7903146, rs698267, rs1696981. We observed no association between rs6983267 and rs16969681 polymorphism and risk of CRC and low association between TCF7L2, rs7903146, polymorphism and risk of CRC. The recessive model of the TCF7L2 rs7903146 had an OR of 1.6 (95% CI 0.058-4.414, P < .05) which means that TT genotype increased the risk and possibility of development of CRC. Our study did not confirm a significant association between TCF7L2 rs7903146, CASC8 rs6983267, and GREM1 rs16969681 with CRC, but emphasizes the possibility of existence of a high risk of CRC development in patients with TT genotype of rs7903146.

Clinical signs of type 1 diabetes are associated with type 2 diabetes marker transcription factor 7-like 2 polymorphism.

We aimed to assess the distribution of transcription factor 7-like 2 gene TCF7L2 (rs7903146) polymorphism and to find possible associations between TCF7L2 and the characteristics of type 1 diabetes. We studied 190 newly diagnosed type 1 diabetes patients (median age 12.7 years, range 2.0-72.5) and 246 controls (median age 23.8 years, range 1.4-81.5) for TCF7L2 single nucleotide polymorphism. We determined anti-islet autoantibodies, random C-peptide levels, diabetes associated HLA DR/DQ haplotypes and genotypes in all patients. There were no differences in the distribution of TCF7L2 single nucleotide polymorphism between patients and controls. However, patients with in type 1 diabetes, after adjusting for age and sex, subjects carrying C allele were at risk for a C-peptide level lower than 0.5 nmol/L (OR 5.65 [95% CI: 1.14-27.92]) and for zinc transporter 8 autoantibody positivity (5.22 [1.34-20.24]). Participants without T allele were associated with a higher level of islet antigen-2 autoantibodies (3.51 [1.49-8.27]) and zinc transporter 8 autoantibodies (2.39 [1.14-4.99]). The connection of TCF7L2 polymorphism with zinc transporter 8 and islet antigen-2 autoantibodies and C-peptide levels in patients supports the viewpoint that TCF7L2 is associated with the clinical signs and autoimmune characteristics of type 1 diabetes. The mechanisms of the interaction between the TCF7L2 risk genotype and anti-islet autoantibodies need to be studied further.

Association of TCF7L2, CASC8 and GREM1 Polymorphisms in Patients with Colorectal Cancer and Type II Diabetes Mellitus.

Background: The aim of the study is to explore the association between the TCF7L2 rs7903146, CASC8 rs6983267 and GREM1 rs16969681 polymorphisms in patients diagnosed with type 2 diabetes mellitus (T2DM) and colorectal cancer. Methods: Sixty individuals were enrolled in this case-control study: thirty with colorectal cancer and type II diabetes mellitus (T2DM) and thirty healthy control individuals. Real-time PCR was used to determine the genotypes of TCF7L2 rs7903146, CASC8 rs 6983267 and GREM1 rs16969681 in patients with CRC and T2DM and in patients without T2DM and CRC. The Hardy–Weinberg equilibrium was determined in the control group for the genotype distribution of every polymorphism. Results: People carrying the TT genotype of rs7903146, rs6983267 and rs1696981 had a significant association with T2DM and CRC. Moreover, the people with the TT genotype of rs1696981 had a greater risk for T2DM and CRC (OR = 7, CI 0.397–23.347). Conclusions: TCF7L2 rs7903146, CASC8 rs6983267 and GREM1 rs16969681 could be risk factors for the association of T2DM with CRC.

Association of gene polymorphisms with body weight changes in prediabetic patients

BackgroundRecent research has demonstrated that Type 2 Diabetes (T2D) risk is influenced by a number of common polymorphisms, including MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146. Knowledge of the association between these single nucleotide polymorphisms (SNPs) and body weight changes in different forms of prediabetes treatment is still limited. The aim of this study was to investigate the association of polymorphisms within the MC4R, PPARG, and TCF7L2 genes on the risk of carbohydrate metabolism disorders and body composition changes in overweight or obese patients with early carbohydrate metabolism disorders.Methods and resultsFrom 327 patients, a subgroup of 81 prediabetic female patients (48.7 ± 14.8 years) of Eastern European descent participated in a 3-month study comprised of diet therapy or diet therapy accompanied with metformin treatment. Bioelectrical impedance analysis and genotyping of MC4R rs17782313, PPARG rs1801282, and TCF7L2 rs7903146 polymorphisms were performed. The MC4R CC and TCF7L2 TT genotypes were associated with increased risk of T2D (OR = 1.46, p = 0.05 and OR = 2.47, p = 0.006, respectively). PPARG CC homozygotes experienced increased weight loss; however, no additional improvements were experienced with the addition of metformin. MC4R TT homozygotes who took metformin alongside dietary intervention experienced increased weight loss and reductions in fat mass (p < 0.05).ConclusionsWe have shown that the obesity-protective alleles (MC4R T and PPARG C) were positively associated with weight loss efficiency. Furthermore, we confirmed the previous association of the MC4R C and TCF7L2 T alleles with T2D risk.

Possible Role of rs7903146 Polymorphism of the Transcription Factor 7-Like 2 Gene in Genetic Predisposition to Type 2 Diabetes.

&lt;b&gt;Background and Objective:&lt;/b&gt; The association of rs7903146 polymorphism of TCF7L2 gene with Type 2 diabetes mellitus found almost in all ethnic groups. Therefore, the current study focused on estimating this association in the Azerbaijan population for the 1st time. &lt;b&gt;Materials and Methods:&lt;/b&gt; A study was conducted on 110 patients with Type 2 diabetes mellitus and 115 healthy controls. The biochemical parameters were analyzed and calculated with an independent t-test and Fisher exact test. DNA extracted from the blood samples run in PCR. PCR was used to detect the presence of TCF7L2 rs7903146 C/T polymorphism and the products of the PCR were visualized in a 1.5% gel electrophoresis. &lt;b&gt;Results:&lt;/b&gt; According to the obtained data, T allele and TT genotype of rs7903146 polymorphism strongly correlated with the risk for Type 2 diabetes (odds ratio of 1.68 for T allele and p = 0.007, odds ratio of 3.9 for TT genotype, p = 0.0028). These results were adjusted by applying the recessive model (p = 0.003). Moreover, the biochemical parameters also show a significant difference in the fasting glucose level (p = 0.0001), fasting insulin (p = 0.0001), BMI (p = 0.0002) and age (p = 0.015) inpatient and control groups. &lt;b&gt;Conclusion:&lt;/b&gt; Based on the results, the TCF7L2 rs7903146 (C>T) polymorphism is the genetic risk factor related to Type 2 diabetes in the Azerbaijan population.

Abstract #1002380: The Common Variant in the TCF7L2 Gene Is Associated With Adverse Effects in Type 2 Diabetic Patients Treated With Vildagliptin

Currently vildagliptin can be used for treating type 2 diabetes mellitus (T2DM) as a first-line monotherapy. The main adverse drug events which have been reported with the use of vildagliptin include nausea, loss of appetite, diarrhea, peripheral edema, headache, dizziness and upper respiratory infection. This study was conducted to determine possible association between the TCF7L2 rs7903146 (C >T) polymorphism and adverse drug effects (ADE) occurrence among patients with newly diagnosed T2DM treated with vildagliptin.

Evaluation of Candidate SNPs for Type 2 Diabetes Mellitus in Tohid Hospital of Sanandaj.

The allele frequency of 4 SNPs was evaluated in patients with type 2 diabetes mellitus (T2DM) and compared with healthy controls who had records in Tohid Hospital of Sanandaj. This case-control study was performed on 100 T2DM patients and 100 healthy controls with matched gender and age. After DNA extraction, allele frequency of 4 variant genotypes was evaluated using Tetra-Arms technique. Then, logistic regression analysis was used to calculate the odds ratio. Data analysis was done using SPSS 20 software and the level of significance was less than 0.05. There were no significant relationships between CASQ1 rs2275703A/C and CTLA4 rs231775A/G polymorphisms and T2DM mellitus in the studied population. Also, CC and CT genotypes of the TCF7L2 rs7903146 C/T polymorphism confirmed a T2DM risk factor in the studied population. At the ATF6 rs2070150 C/G polymorphisms, the frequency of GC allele was higher in the control group than in the patient group, and these differences were also statistically significant at the level of alleles in the experimental and control groups. The CC and CT genotype of TCF7L2 rs7903146 polymorphism and GC genotype of ATF6 rs207015 were the risk factor for T2DM in this population.

TCF7L2 rs7903146 polymorphism modulates the association between adherence to a Mediterranean diet and the risk of gestational diabetes mellitus

ObjectiveThere is sparse evidence for the impact of gene-diet interaction on gestational diabetes mellitus (GDM) onset. Recent findings have shown that late first-trimester high adherence to a Mediterranean diet (MedDiet) pattern is associated with a GDM risk reduction. The aim of this study was to investigate if this effect could be modulated by TCF7L2 rs7903146 polymorphism.Research design and methods: A total of 874 pregnant women participants in the St Carlos GDM prevention study, were stratified into three groups defined as “High,5–6 on targets”, “Moderate, 2–4 on targets” or “Low, 0–1 on targets” adherence to Mediterranean diet according to late first-trimester compliance with six food targets: >12 servings/week of vegetables, >12 pieces/week of fruits, <2 servings/week of juice, >3 servings/week of nuts, >6 days/week and >40 mL/day consumption of extra virgin olive oil. All patients were genotyped for rs7903146 using Taqman technology. ResultsLogistic regression analysis revealed that the risk of developing GDM in those with high adherence versus low adherence was significantly reduced only in carriers of the T-allele (CT + TT), with an adjusted odds ratio of 0.15 (95% CI:0.05–0.48). This effect was not observed in CC carriers. Interaction analysis yielded significant rs7903146-MedDiet interaction in GDM risk (p < 0.03) ConclusionsWomen carrying the rs7903146 T-allele who highly adhere to a MedDiet early in pregnancy have lower risk of developing GDM than CC carriers. This reinforces the importance of identifying patients at risk of GDM who would be especially sensitive to nutritional interventions based on their genetic characteristics.

Heritability and Genetics of Type 2 Diabetes Mellitus in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

Objectives Sub-Saharan Africa (SSA) is observing an accelerating prevalence rate of type 2 diabetes mellitus (T2DM) influenced by gene-environment interaction of modifiable and nonmodifiable factors. We conducted a systematic review and meta-analysis on the heritability and genetic risk of T2DM in SSA. Methods We reviewed all published articles on T2DM in SSA between January 2000 and December 2019 and available in PubMed, Scopus, and Web of Science. Studies that reported on the genetics and/or heritability of T2DM or indicators of glycaemia were included. Data extracted included the study design, records of family history, pattern and characteristics of inheritance, genetic determinants, and effects estimates. Results The pattern and characteristics of T2DM heritability in SSA are preference for maternal aggregation, higher among first degree compared to second-degree relatives; early age-onset (<50 years), and inherited abnormalities of beta-cell function/mass. The overall prevalence of T2DM was 28.2% for the population with a positive family history (PFH) and 11.2% for the population with negative family history (NFH). The pooled odds ratio of the impact of PFH on T2DM was 3.29 (95% CI: 2.40-4.52). Overall, 28 polymorphisms in 17 genes have been investigated in relation with T2DM in SSA. Almost all studies used the candidate gene approach with most (45.8%) of genetic studies published between 2011 and 2015. Polymorphisms in ABCC8, Haptoglobin, KCNJ11, ACDC, ENPP1, TNF-α, and TCF7L2 were found to be associated with T2DM, with overlapping effect on specific cardiometabolic traits. Genome-wide studies identified ancestry-specific signals (AGMO-rs73284431, VT11A-rs17746147, and ZRANB3) and TCF7L2-rs7903146 as the only transferable genetic risk variants to SSA population. TCF7L2-rs7903146 polymorphism was investigated in multiple studies with consistent effects and low-moderate statistical heterogeneity. Effect sizes were modestly strong [odds ratio = 6.17 (95% CI: 2.03-18.81), codominant model; 2.27 (95% CI: 1.50-3.44), additive model; 1.75 (95% CI: 1.18-2.59), recessive model]. Current evidence on the heritability and genetic markers of T2DM in SSA populations is limited and largely insufficient to reliably inform the genetic architecture of T2DM across SSA regions.

Investigations of Associations between Seven Gene Polymorphisms and Gestational Diabetes Mellitus: Evidence From a Meta-Analysis

Background: Associations of polymorphisms in transcription factor 7 like 2 (TCF7L2), tumor necrosis factor-α (TNF-α), vitamin D receptor (VDR), and interleukin-10 with gestational diabetes mellitus (GDM) were already reported by several publications. Objectives: The aim of this meta-analysis was to better clarify associations between these polymorphisms and GDM by combing the results of all relevant publications. Methods: Eligible publications were searched from Pubmed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies. Results: Thirty-nine studies were included in this study. Combined results revealed that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms were all significantly associated with susceptibility to GDM in the total population. In subgroup analyses, we obtained similar positive findings for rs290487, rs7903146, rs1800629, and rs2228570 polymorphisms in Asians, and positive results were also observed for rs7901695, rs7903146, and rs12255372 polymorphisms in Caucasians. Conclusions: Collectively, this meta-analysis proved that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms may confer susceptibility to GDM in certain populations.

TCF7-L2 rs7903146 polymorphism in metabolic syndrome with and without acute coronary syndrome.

To determine the frequency and association of single nucleotide polymorphism of transcription cell factor7-like2 rs7903146 (C>T) in metabolic syndrome patients with and without acute coronary syndrome. The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July to December 2017. Patients of metabolic syndrome with and without acute coronary syndrome were selected from Sheikh Zayed Hospital, Lahore, and the Punjab Institute of Cardiology, Lahore. Healthy subjects were enrolled to act as controls. A fasting blood sample of 8ml was taken for deoxyribonucleic acid extraction and estimation of biochemical parameters. Single nucleotide polymorphism of transcription cell factor7-like2 rs7903146 C>T was determined using restriction fragment length polymorphism. SPSS 22 was used for data analysis. Of the 500 subjects, 200(40%) were group A patients without acute coronary syndrome, 100(20%) were in group B with acute coronary syndrome and 200(40%) were group C controls. Overall, 385(77%) were males and 115(23%) were females. The frequency of CC variant in group A was 35(17.5%) and in group C 22(11%), while CT was 32(16%) and 65(32.5%), and TT was 133(66.5%) and 113(56.5%), respectively. There was significant association of TT genotype with increased risk of metabolic syndrome (p=0.031), and CC genotype had no association (p=0.121). There was no significant difference of genotype frequency between groups A and B (p=0.246), but TT variant was significantly higher in group A compared to group B (p=0.009). TT genotype of transcription cell factor7-like2 rs7903146 C>T was found to be associated with increased risk of metabolic syndrome in patients without acute coronary syndrome compared to those with acute coronary syndrome and healthy controls.

Association between the UBE2Z rs46522 and TCF7L2 rs7903146 polymorphisms with type 2 diabetes in south western Iran.

Transcription factor 7-like 2 Protein (TCF7L2) has a strong role in the pathogenesis of type 2 diabetes mellitus (T2DM). Association between rs7903146 and T2D risk reported in some of populations. Also many loci such as UBE2Z rs46522 are affecting by TCF7L2 transcription factor have been found associated with T2D. The present study aimed to evaluate association of the SNPs with risk of T2D among our population. This case-control study was conducted on 150 T2D patients and 150 healthy people (as a control group) in south western Iran. Genotyping was performed by PCR-RFLP. The frequency of genotypes showed no remarkable difference between T2DM patients and control group. The odds ratios of rs7903146 (C/T) polymorphism for CC and TC genotypes were 1.9 (95% CI, 0.85 to 4.24; P=0.12) and 0.81 (95% CI, 0.47 to 1.38; P=0.43) compared with the TT genotype, respectively. The odds ratios of rs46522 (C/T) polymorphism for TT and TC genotypes were 1.75 (95% CI, 0.86 to 3.59; P=0.13) and 1.38 (95% CI, 0.81to 2.35; P=0.24) compared with the CC genotype, respectively. Our study indicates no association of T2D in south western Iran with the rs7903146 and rs46522 variants.

Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism

Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.

Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes

BackgroundGlucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity.ObjectivesTo evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the TCF7L2 variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide.MethodsIntervention study. Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8 weeks.ResultsPatients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0–180 min before treatment and a similar decrease after treatment (p < 0.001). Before exenatide, insulin levels at 30–120 min were higher in CT/TT versus CC subjects (p < 0.05). After treatment with exenatide, only CT/TT individuals demonstrated insulin reduction at 30–180 min during the meal test (p < 0.05). Patients with the CC genotype presented no differences in insulin concentrations before and after treatment. The areas under the glucagon curve between 0 and 180 min were similar before treatment and reduced after treatment in both groups (p < 0.001).ConclusionsThe presence of the TCF7L2 rs7903146 T allele in patients with T2DM was associated with increased secretion of insulin response to a mixed-meal test. Furthermore, after treatment with exenatide, only the carriers of the T allele showed significantly decreased postprandial plasma insulin peak levels comparing with non carriers.

Genetic variation in TCF7L2 rs7903146 and history of GDM negatively and independently impact on diabetes-associated metabolic traits

AimsGestational diabetes (GDM) is recognized as a major risk factor for the development of type 2 diabetes (T2DM) later in life. Risk allele carriers at TCF7L2 rs7903146 have increased susceptibility for both GDM and T2DM. We hypothesized that carrying TCF7L2 risk alleles would further aggravate the negative impact of a positive history for GDM on metabolic traits related to T2DM later in life. Methods210 women with a confirmed history of gestational diabetes and 810 controls without evidence for GDM underwent standardized 75 g oral glucose tolerance tests (OGTT). Liver fat was quantified in a subset of subjects (n = 444) using magnetic resonance spectroscopy. Results504 women were homozygous or heterozygous risk allele carriers. The risk allele carriers had a higher risk for GDM (p = 0.0076, OR 1.52, 95% CI 1.11–2.06). Multivariable regression analysis demonstrated that both a history of GDM, or carrying a TCF7L2 risk allele resulted in lower insulin secretion, impaired proinsulin processing and higher fasting and 2-hour glucose levels. Liver fat content was not associated with either a history of GDM or a TCF7L2 risk genotype. There was no significant interaction (all p > 0.05) between history of GDM and TCF7L2 risk alleles on all diabetes-associated metabolic traits tested. ConclusionThe TCF7L2 rs7903146 polymorphism is a risk factor for gestational diabetes. However, the additional presence of TCF7L2 rs7903146 risk alleles does not further aggravate the negative impact of a history of gestational diabetes on metabolic traits related to T2DM.

TCF7L2-rs7903146 polymorphism modulates the effect of artichoke leaf extract supplementation on insulin resistance in metabolic syndrome: a randomized, double-blind, placebo-controlled trial

BackgroundTranscription factor 7-like 2 (TCF7L2)-rs7903146 polymorphism is associated with increased risk of type 2 diabetes. The response of insulin and insulin resistance to artichoke leaf extract (ALE) may be affected by TCF7L2-rs7903146 polymorphism. ObjectiveThis study examined the effects of ALE supplementation on metabolic parameters of the TCF7L2-rs7903146 polymorphism in patients with metabolic syndrome (MetS). Design, setting, participants and interventionsThis double-blind clinical trial was conducted on 80 patients with MetS in Sina Clinic, Khoy, Iran. The patients were randomized into ALE or placebo groups to receive either ALE (1800 mg/d as four tablets) or matching placebo for 12 weeks. Main outcome measuresAnthropometric indices, blood pressure, glucose and lipid profile levels were measured before and after the study. Moreover, patients were genotyped for TCF7L2 polymorphism. ResultsALE supplementation decreased insulin level and the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with the TT genotype of TCF7L2-rs7903146 polymorphism (P < 0.05). There was no significant interaction between blood pressure, glucose and lipid profile response to ALE supplementation. ConclusionThe responses of insulin and HOMA-IR to ALE supplementation have shown an interaction with single-nucleotide polymorphism rs7903146 in TCF7L2. Trial registrationIranian Registry of Clinical Trial IRCT201409033320N9.

Association between Transcription Factors 7-like 2 (rs7903146) Polymorphism and Some Renal Biomarkers with Type 2 Diabetic Nephropathy Complications

Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is infuenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iraqi populations Conducted in this study was to investigate the possible role TCF7L2 rs7903146 (C/G) variant on susceptibility of T2DM among Iraqi type 2 diabetic patients with nephropathy complications and its relations with some type of kidney biomarkers. This case-control study included 100 T2DM patients and 100 patient with kidney failure 100 healthy person (control group). The results confrm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Iraqi an populations.

Effects of artichoke leaf extract supplementation on metabolic parameters in women with metabolic syndrome: Influence of TCF7L2‐rs7903146 and FTO‐rs9939609 polymorphisms

The metabolic syndrome (MetS) is a multicomponent condition with a complex etiology involving genetic and environmental factors. Artichoke leaf extract (ALE) has shown favorable effects on lipid and glucose metabolism. The present study aimed to investigate the effects of ALE supplementation on metabolic parameters in women with MetS, using a nutrigenetics approach. In this double-blind randomized clinical trial, 50 women (aged 20-50years) with MetS were randomly allocated into the two groups: "ALE group" (received 1,800mg hydroalcoholic extract of artichoke as four tablets per day) and "placebo group" (received placebo consisted of corn starch, lactose, and avicel as four tablets per day) for 12weeks. The biochemical and anthropometric parameters were determined before and after the intervention. The FTO-rs9939609 and the TCF7L2-rs7903146 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In carriers of A allele of the FTO-rs9939609, ALE supplementation resulted in a statistically significant decrease in serum triglyceride level compared with placebo (-19.11% vs. 10.83%; p<.05), with no other significant differences between the two groups. The TCF7L2-rs7903146 polymorphism showed no interaction with response to ALE (p>.05). These findings suggest that ALE supplementation may improve serum triglyceride level in A allele genotype of FTO-rs9939609 polymorphism in women with MetS.

Association between rs7903146 and rs12255372 polymorphisms of transcription factor 7-like 2 gene and polycystic ovary syndrome: a systematic review and meta-analysis.

The present systematic review and meta-analysis of case-control studies examines the associations between rs7903146 and rs12255372 polymorphisms of the TCF7L2 gene and PCOS. A search of the literature published until August 2014 was carried out in PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and LILACS. There were no other limits except for the end date. We included observational studies with women of any age diagnosed with PCOS and healthy controls that analyzed polymorphisms rs7903146 and rs12255372. We included case-control or cross-sectional studies analyzing polymorphism rs7903146 or rs12255372 in women with PCOS and healthy controls. Eighteen studies were identified after the primary literature search and seven articles were included in the meta-analysis. All employed Rotterdam criteria for the diagnosis of PCOS. The genotypic distributions in the control groups were in agreement with Hardy-Weinberg equilibrium in all studies. The pooled population included Asian descendents (Chinese, Korean), Caucasians from southern Brazil, Tunisian, and European populations (British/Irish, Northern Finns, Greeks, Czechs), including 1,892 women with PCOS and 2,695 controls. There were no significant associations between PCOS and TCF7L2 rs7903146 or rs12255372 polymorphisms, irrespective of whether allele contrast, additive, dominant, or recessive models of inheritance were used. Furthermore, no significant associations were found after stratification for ethnicity (Asian or non-Asian). There was no significant heterogeneity between studies and no publication bias. The present results suggest that rs7903146 T allele or rs12255372 is not associated with risk for PCOS in non-Asian or Asian women. This systematic review and meta-analysis are registered in PROSPERO under number CRD42013005930.

The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil.

The aim of this study was to investigate the association between the rs7903146 (C/T) polymorphism in the TCF7L2 gene and type 2 diabetes mellitus, in a Southern-Brazilian population. The TCF7L2 rs7903146 polymorphism was genotyped in 953 type 2 diabetic patients and 535 non-diabetic subjects. All subjects were white. The polymorphism was genotyped by Real-Time PCR using TaqMan MGB probes (Life Technologies). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for additive, recessive and dominant inheritance models. Genotype and allele frequencies of the rs7903146 polymorphism differed significantly between type 2 diabetic patients and non-diabetic subjects (P = 0.001 and P = 0.0001, respectively). The frequency of the minor allele was 38% in type 2 diabetes group and 31% in non-diabetic subjects, and this allele was significantly associated with type 2 diabetes risk (OR = 1.42, 95% CI 1.15 - 1.76 for the dominant model of inheritance). Moreover, the T/T genotype was associated with a higher risk for type 2 diabetes (OR = 1.83, 95% CI 1.3-2.5) than the presence of only one copy of the T allele (OR = 1.31, 95% CI 1.1-1.6). Both results were adjusted for age and gender. Our results confirm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Southern-Brazil.