Genetic associations between Transcription Factor 7 Like 2 rs7903146 polymorphism and type 2 diabetes mellitus: a meta-analysis of 115,809 subjects

Lou, Liying; Wang, Jingjing; Wang, Jing

doi:10.1186/s13098-019-0451-9

Cited by 16 publications

(12 citation statements)

References 23 publications

(23 reference statements)

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“…Anjum et al [16] in Chinese population, Danquah et al [17] in Ghanaian population, Ezzidi et al [18] in Tunisian population, and Assmann et al [19] in Brazilian population came to the same conclusion of the significance of association of the TCF7L2 rs7903146 (C/T) polymorphism and T2DM susceptibility, especially the homozygous TT genotype. A meta-analysis conducted by Lou et al [20] on subjects from different ethnic groups showed a positive correlation of the rs7903146 C/T SNP with T2DM, and this agrees with a previous meta-analysis made by Ding et al [21].…”

Section: Discussionsupporting

confidence: 89%

Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Bahaaeldin

Seif

Hamed

et al. 2020

Dubai Diabetes Endocrinol J

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Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by the incapability of pancreas to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multifactorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β-catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis, and the incretin glucagon-like peptide 1 (GLP-1) gene. Then, TCF7L2 gene seems to affect diabetes susceptibility through B-cell dysfunction that is why we studied its association with T2DM in particular. Objectives: To investigate the potential association of the transcription factor 7-like-2 (TCF7L2) rs7903146 (C/T) gene polymorphism in patients with T2DM. Methods: A case-control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non-diabetic healthy controls age- and sex-matched with the patients. All subjects underwent full history taking; thorough clinical examination; routine laboratory investigations including hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of TCF7L2 gene polymorphism by qRT-PCR. Results: The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68–2.6) and the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49–2.7); however, they were statistically insignificant (p value >0.05). Conclusion: Our study did not confirm the presence of significant association between the TCF7L2 rs7903146(C/T) polymorphism and T2DM; however, it pointed out the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.

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Section: Discussionsupporting

confidence: 89%

Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Bahaaeldin

Seif

Hamed

et al. 2020

Dubai Diabetes Endocrinol J

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“…23 So far, the data suggest that the allelic frequencies of the rs7903146 SNP and possibly, the effect size of this SNP are variable worldwide. 14 Regarding the Greek population, apart from a study by Katsoulis et al 36 in which the role of TCF7L2 variants in the development of impaired glucose metabolism (including impaired fasting glucose [IFG] or T2DM) in patients with metabolic syndrome (MS) was investigated, the present study is the first report of an association between TCF7L2 rs7903146 variants and prediabetes/T2DM. Christopoulos et al 37 investigated the role of the rs7903146 variant in women with polycystic ovary syndrome, while Pappa et al 38 and Potasso et al 39 examined the association with gestational diabetes mellitus (GDM).…”

Section: Discussionmentioning

confidence: 85%

“…23 So far, the data suggest that the allelic frequencies of the rs7903146 SNP and possibly, the effect size of this SNP are variable worldwide. 14 Regarding the Greek population, apart from a study by Katsoulis et al 36 in which the role of TCF7L2 variants in the In the present study, the participants were separated into two subgroups based on their HbA1c levels. One subgroup comprised of patients exhibiting normal HbA1c values (HbA1c< 5.7%) while the other subgroup consisted of patients identified with hyperglycemia (HbA1c ≥ 5.7%).…”

Section: Discussionmentioning

confidence: 86%

“…More specifically, potential multiplicative genetic model for four single nucleotide polymorphisms (SNPs) of the TCF7L2 gene (rs7901695 T-to-C, rs11196205 G-to-C, rs12255372 G-to-T, and rs7903146C-to-T) among different ethnic populations is suggested allowing for the last two variants to be taken as reference loci in order to explore T2DM susceptibility. 12,14 The aim of present study was to screen dental patients of Greek origin for prediabetes/diabetes and identify the possible relation of TCF7L2 rs7903146 genotype with this condition and their periodontal status.…”

Section: Introductionmentioning

confidence: 99%

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Interaction between TCF7L2 rs7903146 Genotype, HbA1c Levels, and the Periodontal Status of Dental Patients

et al. 2021

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Objective The aim of the study was to investigate the potential interaction between TCF7L2 rs7903146 genotype, which is implicated for type-2 diabetes mellitus genetic susceptibility, HbA1c levels, and the periodontal status of dental patients. Materials and Methods HbA1c levels, clinical periodontal parameters (probing depth, clinical attachment level, bleeding on probing, and plaque index), and several parameters (such as body mass index [BMI], smoking habits, education level, and age) were recorded in 150 patients who fulfilled the criteria for screening for prediabetes/diabetes of the Centers for Disease Control and Prevention. DNA was extracted and the TCF7L2 single nucleotide polymorphism (SNP) rs7903146 was genotyped in all participants. Results Thirty-one patients out of 150 tested were found with unknown hyperglycemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between patients displaying HbA1c < 5.7 and ≥ 5.7% (Pearson’s Chi-square test, p > 0.05). Regarding periodontal parameters and differences between subgroups (HbA1c levels ≥ 5.7 and HbA1c levels < 5.7), statistically significant differences were observed for probing depth (3.20 ± 0.94 vs. 2.81 ± 0.78 mm), clinical attachment level (3.54 ± 1.20 vs. 3.18 ± 1.06 mm) and bleeding on probing (0.62 ± 0.25 vs. 0.50 ± 0.24%) with hyperglycemic patients exhibiting worse periodontal conditions (Mann–Whitney test p < 0.05). The allelic and genotype frequencies for the transcription factor 7-like 2 (TCF7L2) gene, SNPs 7903146 did not exhibit a significant difference between the HbA1c > 5.7 and HbA1c < 5.7 groups and the periodontitis and nonperiodontitis subgroups respectively (Fisher’s exact test >0.05). Statistical Analysis Patient characteristics and their association with prediabetes were tested by Pearson’s Chi-square test (asymptotic, two sided). Differences of periodontal parameters between subgroups were tested with the Mann–Whitney U-test. The associations of allele and genotype frequencies in the patient and control groups were analyzed using the Fisher’s exact test of independence.The significance level was set at the 0.05 for all tests. Conclusion A statistically significant association between TCF7L2 rs7903146 genotype and periodontal condition or HbA1c levels was not observed in contrast to statistically significant differences of clinical parameters of periodontitis in patients with hyperglycemia.

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“…Authors additionally noted that there is also an elevated proinsulin to insulin ratio. Meta-analysis on 115,809 subjects [10] based on 68 studies also revealed that there is a strong association between T2D and the rs7903146 polymorphism.…”

Section: Introductionmentioning

confidence: 95%

Genetic Variations Influencing Glucose Homeostasis and Insulin Secretion and their Associations with Autism Spectrum Disorder in Kazakhstan

2021

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There is a complex interaction between glucose and insulin homeostasis pathways, diabetes and autism spectrum disorder (ASD). It is known that neuronal migration pathways may be interrupted by intrauterine hyperinsulinemia and hyperglycemia. Moreover, neonatal hypoglycemia which is related to mitochondrial dysfunction has a potential role that influences ASD pathogenesis [6,7]. We present here a preliminary case-control study on children and adolescents (8 -15 years old) with and without autism spectrum disorder examining the association between genetic polymorphisms impacting glucose and insulin homeostasis and autism spectrum disorder in Kazakhstan. Methods:In this case-control study looking at 211 samples, associations of glucose and insulin homeostasis gene polymorphisms of 10 genes and demographic variables with autism spectrum disorder were examined. Fisher's exact test and multivariate logistic regression models were used to find associations between polymorphisms and other predictors.Results: Preliminary results suggest that there is a complex relation between autism spectrum disorder and genetic variations that are associated with impaired glucose and insulin homeostasis susceptibility. There is a significant association of the T allele of ADIPOQ (rs1501299) (OR=1.75, 95% CI:1.04-2.93, p-value=0.035); the T allele of GCKR (rs1260326) (OR=0.6, 95% CI:0.39-0.93, p-value=0.023); the T allele of SLC30A8 (rs13266634) (OR=1.77, 95% CI:1.12-2.78, p-value=0.014); and the recessive GG genotype of rs10757278 (CDKN2B) (OR=2.58, 95% CI: 1.24-5.36, p-value=0.011) with autism spectrum disorder in the Kazakhstan population. Conclusion:Overall, this preliminary study revealed that there is evidence of significant associations between glucose and insulin homeostasis gene polymorphisms and autism spectrum disorder susceptibility in Kazakhstan and further study in this area to further verify this, is needed.

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Genetic associations between Transcription Factor 7 Like 2 rs7903146 polymorphism and type 2 diabetes mellitus: a meta-analysis of 115,809 subjects

Cited by 16 publications

References 23 publications

Transcription Factor 7-Like-2 (<b><i>TCF7L2</i></b>) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Transcription Factor 7-Like-2 (<b><i>TCF7L2</i></b>) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

Interaction between TCF7L2 rs7903146 Genotype, HbA1c Levels, and the Periodontal Status of Dental Patients

Genetic Variations Influencing Glucose Homeostasis and Insulin Secretion and their Associations with Autism Spectrum Disorder in Kazakhstan

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