Genetic variants associated with fasting glucose levels in the Brazilian population: a review of studies of European-identified polymorphisms

Variantes genéticas associadas aos níveis de glicose em jejum na população brasileira: uma revisão de estudos de polimorfismos identificados em europeus

ABSTRACT

Objective

Impaired fasting glucose is a well-known risk factor for diabetes, and has been linked to other conditions, such as cardiovascular and Alzheimer’s disease. Whether these associations imply causation remains to be established. Observational studies are often afflicted by confounding and reverse causation, making them less than ideal for demonstrating causal relationships. Genetically-informed methods like Mendelian randomization, which are less susceptible to these biases, can be implemented. Mendelian randomization uses genetic variants as proxies (or instrumental variables) for modifiable exposures, testing their association with disease outcomes. However, since most genetic proxies have been described in European populations, applying Mendelian randomization in the Brazilian population necessitates the identification of locally relevant instruments. We investigated genetic variants associated with fasting glucose that were discovered in genome-wide association studies of Europeans and have also been examined in Brazil. The aim of our study was to define whether these variants served as proxies for fasting glucose in Brazil too.

Methods

We carried out an exhaustive literature search using databases of published research articles and a repository of Brazilian theses and dissertations.

Results

We examined a total of 38 papers and 27 dissertations/theses, published between 1997 and 2022, involving 21888 participants. We found few results for impaired fasting glucose, as opposed to many reports on the association of the selected genetic variants with diabetes. The genes GCK and TCF7L2 prevailed in the analyses, although studies on GCK were mainly related to Maturity-Onset Diabetes of the Young rather than to common diabetes conditions.

Conclusion

Additional studies with improved reporting of findings are imperative to elucidate the genetic predictors of fasting glucose (and possibly other risk factors) in Brazil.

Keywords:
Brazil; Diabetes Mellitus; Genome-wide association studies; Mendelian randomization; Single nucleotide polymorphisms