TCF7L2variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population

Abstract

BackgroundGenetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.MethodsWe genotyped the single nucleotide polymorphisms (SNP) rs7903146 of the TCF7L2 gene in 560 patients with known coronary disease enrolled in the MASS II (Medicine, Angioplasty, or Surgery Study) Trial and in 1,449 residents of Vitoria, in Southeast Brazil. The associations of this gene variant to diabetes risk and metabolic characteristics in these two different populations were analyzed. To access the potential benefit of using this marker for diabetes risk prediction in the general population we analyzed the impact of this genetic variant on a validated diabetes risk prediction tool based on clinical characteristics developed for the Brazilian general population.ResultsSNP rs7903146 of the TCF7L2 gene was significantly associated with type 2 diabetes in the MASS-II population (OR = 1.57 per T allele, p = 0.0032), confirming, in the Brazilian population, previous reports of the literature. Addition of this polymorphism to an established clinical risk prediction score did not increased model accuracy (both area under ROC curve equal to 0.776).ConclusionTCF7L2 rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease. However, the inclusion of this polymorphism in a risk prediction tool developed for the general population resulted in no improvement of performance. This is the first study, to our knowledge, that has confirmed this recent association in a South American population and adds to the great consistency of this finding in studies around the world. Finally, confirming the biological association of a genetic marker does not guarantee improvement on already established screening tools based solely on demographic variables.

Association of the rs7903146 single nucleotide polymorphism at the Transcription Factor 7-like 2 (TCF7L2) locus with type 2 diabetes in Brazilian subjects

“…The odds ratio for the association with genotype TT (recessive model) were 3.92 (CI 95%; 1.49-10.3); and for T allele 1.51 (CI 95%; 1.03-2.21), similar to that reported in the previous study involving the Brazilian population (28), as well as in other populations (10,25,32). The T allele was significantly more frequent in T2D patients than in controls (35.8% versus 27%; p = 0.032).…”

“…reported that the T allele of rs7903146 SNP at the TCF7L2 locus is associated with a 1.57 increase in the risk of T2D in a sample of patients with documented multivessel coronary artery disease from the multivessel coronary disease patient studies (MASS II Study) in Southeastern Brazil, although this genetic variant did not increase the accuracy of a validated diabetes risk prediction score for the Brazilian population (28). We have previously shown a 37% frequency of the T allele of rs7903146 SNP at the TCF7L2 locus in a group of 104 healthy young volunteers (mean age of 27.7 ± 11 years) randomly selected in Brasilia, the capital of Brazil (29).…”

Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans

“…Similarly, this polymorphism was found associated with diabetes in several works carried out in admixed populations from other Latin American countries (9,(23)(24)(25)28,29,31,32). However, Barros and cols.…”

“…Moreover, among Latin American countries there are only reports on the association of TCF7L2 polymorphisms and T2DM from Colombia (23), Brazil (24)(25)(26)(27)(28) and Mexico (9,(29)(30)(31)(32). Latin American populations are characterized by high socioeconomic and genetic heterogeneity with varying degrees of ancestral population proportions from country to country, thus more studies are needed exploring the basis of T2DM susceptibility from these mixed populations.…”

Genomic Risk Profiling: Attitudes and Use in Personal and Clinical Care of Primary Care Physicians Who Offer Risk Profiling

“…Although interventions based on individual genomic risk could potentially lead to adoption of risk reduction behaviors, screening and/or early diagnosis and improved morbidity and mortality, the validity of genomic risk information and likelihood of improving health outcomes is unclear [2][3][4] . Recent data cast doubt on the utility and/or added value of genetic testing [5][6][7][8][9][10][11] . Furthermore, many primary care physicians (PCPs) have limited knowledge of genetic testing or how to translate test results into clinically relevant information [12][13][14][15][16] .…”