Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects

Saadi, Hanane; Nagelkerke, Nicolaas; Carruthers, S. George; Benedict, Sheela; Abdulkhalek, Samar; Reed, Richard; Lukic, Miodrag L.; Nicholls, M. Gary

doi:10.1016/j.diabres.2008.01.008

Cited by 89 publications

(76 citation statements)

References 32 publications

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“…However, new studies in different ethnic groups have reported inconsistent results, including in Chinese and North American Native American populations (Guo et al, 2007;Ren et al, 2008). These studies were supported by a lack of association between T2D and the TCF7L2 SNP rs7903146 and a marginal association of rs12255372 in a United Arab Emirates population (Saadi et al, 2008). In addition, there was no association of either SNP with Saudi Arabian diabetic patients (Alsmadi et al, 2008).…”

Section: Discussionmentioning

confidence: 52%

“…However, conflicting results have been reported in populations from China, Saudi Arabia, and the United Arab Emirates, as well as in the Native American population of North America (Guo et al, 2007;Alsmadi et al, 2008;Ren et al, 2008;Saadi et al, 2008). Moreover, although an association between the TCF7L2 SNPs rs7903146 and rs12255372 and T2D has been investigated in several studies of Caucasian populations, there have been relatively few studies of mixed populations, such as Brazilians (Marquezine et al, 2008;Franco et al, 2011;Barra et al, 2012;Furgeri et al, 2012).…”

Section: Introductionmentioning

confidence: 94%

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Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil

Barros¹,

Araujo-Neto²,

Lopes³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Approximately 200 million people suffer from type 2 diabetes (T2D) worldwide, and the rapid increase in the prevalence of this disease is likely a result of multiple environmental factors, such as increased food intake and decreased physical activity in genetically predisposed individuals. Different population studies have demonstrated a strong association of two polymorphic variations in the TCF7L2 gene, the noncoding single nucleotide polymorphisms (SNPs) rs7903146 (C/T) and rs12255372 (G/T), with T2D. Herein, we analyzed the association of these SNPs with T2D in a population from northeastern Brazil. Our results showed that the genotype and allele frequencies in TCF7L2 rs7903146 and rs12255372 were similar in the patient and control groups (P > 0.05). In addition, the allele frequencies were not significantly associated with T2D risk [rs7903146: odds ratio (OR) = 0.95, 95% confidence interval (CI) = 0.52-1.76, P = 1.00, and rs12255372: OR = 1.38, 95%CI = 0.72-2.62, P = 0.41]. These data suggest that the TCF7L2 SNPs rs7903146 and rs12255372 may not significantly contribute to T2D susceptibility in this population. However, our results may reflect the small number of subjects. Alternatively, these results may be attributable to specific ethnic effects, as most of the previously reported associations were demonstrated with predominantly European populations. To reach a definitive conclusion on the role of such gene variants for T2D in mixed populations, additional efforts are necessary to replicate this study with larger populations from areas with more ethnic heterogeneity.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 94%

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil

Barros¹,

Araujo-Neto²,

Lopes³

et al. 2014

Genet. Mol. Res.

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“…12 In addition, association between this polymorphism and type 2 diabetes has been well demonstrated in African Americans and in West Africans, 21,22 but data are less consistent in northern African populations. [23][24][25] Older age, BMI, and tacrolimus use were other significant independent risk factors in white patients. Steroid boluses, given for acute rejection episodes, also accounted for the risk for developing NODAT.…”

Section: Discussionmentioning

confidence: 99%

TCF7L2 Polymorphism Associates with New-Onset Diabetes after Transplantation

Ghisdal¹,

Baron

Meur

et al. 2009

Journal of the American Society of Nephrology

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New-onset diabetes after transplantation (NODAT) is a serious and frequent complication in transplant recipients. Whether NODAT shares the same susceptibility genes as type 2 diabetes is unknown. In this multicenter study, we genotyped 1076 white patients without diabetes at transplantation for 11 polymorphisms that associate with type 2 diabetes. We defined NODAT as a fasting plasma glucose Ն126 mg/dl on at least two occasions or de novo hypoglycemic therapy. We compared clinical and genetic factors between patients who developed NODAT within 6 mo of transplantation (n ϭ 118; incidence 11%) and patients without diabetes (n ϭ 958). In multivariate analysis, NODAT significantly associated with the following characteristics: TCF7L2 polymorphism (odds ratio [OR] 1.60 per each T allele; P ϭ 0.002), age (OR 1.03 per year; P Ͻ 0.001), body mass index at transplantation (OR 1.09 per unit; P Ͻ 0.001), tacrolimus use (OR 2.26; P Ͻ 0.001), and the occurrence of a corticoid-treated acute rejection episode (OR 2.78; P Ͻ 0.001). In summary, our data show that the TCF7L2 rs7903146 polymorphism, a known risk factor for type 2 diabetes in the general population, also associates with NODAT.

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“…No replication was observed at rs7903146, a variant at TCF7L2 that has been strongly associated with T2D risk in most populations (Zeggini et al, 2008), including a Palestinian population (Ereqat et al, 2010). Other studies of rs7903146 in Arab populations of Saudi and Emirati origin also showed weak or no association with T2D (Alsmadi et al, 2008;Saadi et al, 2008). Whilst the power of our study may have limited our ability to replicate top hits found in conventional populationbased case-control GWAS for T2D, there is increasing support (Coventry et al, 2010;Dickson et al, 2010) for the possibility that functional variants that are rare in the general population may be enriched through highly shared ancestry, identity-bydescent and linkage in the kind of extended pedigree that we have used in our discovery GWAS.…”

Section: Discussionmentioning

confidence: 94%

A Genome‐Wide Search for Type 2 Diabetes Susceptibility Genes in an Extended Arab Family

Safar

Cordell

Jafer

et al. 2013

Annals of Human Genetics

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SummaryTwenty percent of people aged 20 to 79 have type 2 diabetes (T2D) in the United Arab Emirates (UAE). Genome-wide association studies (GWAS) to identify genes for T2D have not been reported for Arab countries. We performed a discovery GWAS in an extended UAE family (N = 178; 66 diabetic; 112 healthy) genotyped on the Illumina Human 660 Quad Beadchip, with independent replication of top hits in 116 cases and 199 controls. Power to achieve genome-wide significance (commonly P = 5 × 10 −8 ) was therefore limited. Nevertheless, transmission disequilibrium testing in FBAT identified top hits at Chromosome 4p12-p13 (KCTD8: rs4407541, P = 9.70 × 10 −6 ; GABRB1: rs10517178/rs1372491, P = 4.19 × 10 −6 ) and 14q13 (PRKD1: rs10144903, 3.92 × 10 −6 ), supported by analysis using a linear mixed model approximation in GenABEL (4p12-p13 GABRG1/GABRA2: rs7662743, P adj-agesex = 2.06 × 10 −5 ; KCTD8: rs4407541, P adj-agesex = 1.42 × 10 −4 ; GABRB1: rs10517178/rs1372491, P adj-agesex = 0.027; 14q13 PRKD1: rs10144903, P adj-agesex = 6.95 × 10 −5 ). SNPs across GABRG1/GABRA2 did not replicate, whereas more proximal SNPs rs7679715 (P adj-agesex = 0.030) and rs2055942 (P adj-agesex = 0.022) at COX7B2/GABRA4 did, in addition to a trend distally at KCTD8 (rs4695718: P adj-agesex = 0.096). Modelling of discovery and replication data support independent signals at GABRA4 (rs2055942: P adj-agesex-combined = 3 × 10 −4 ) and at KCTD8 (rs4695718: P adj-agesex-combined = 2 × 10 −4 ). Replication was observed for PRKD1 rs1953722 (proxy for rs10144903; P adj-agesex = 0.031; P adj-agesex-combined = 2 × 10 −4 ). These genes may provide important functional leads in understanding disease pathogenesis in this population.

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Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects

Cited by 89 publications

References 32 publications

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil

TCF7L2 Polymorphism Associates with New-Onset Diabetes after Transplantation

A Genome‐Wide Search for Type 2 Diabetes Susceptibility Genes in an Extended Arab Family

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