Associations Between TCF7L2, PPARγ, and KCNJ11 Genotypes and Insulin Response to an Oral Glucose Tolerance Test: A Systematic Review

Scope: Insulin responses to standardized meals differ between individuals. This variability may in part be explained by genotype. This systematic review evaluates associations between genotype and insulin response to an oral glucose tolerance test (OGTT) in terms of insulin area under the curve (AUC). Methods and results: Three electronic databases (Web of Science, Embase, PubMed) were searched for studies investigating associations between insulin AUC after an OGTT and single nucleotide polymorphisms (SNPs) belonging to the transcription factor 7 like 2 (TCF7L2) gene, the peroxisome proliferator‐activated receptor gamma (PPARγ) gene, or the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene in persons without diabetes. A total of 5199 articles were identified, of which 38 were included. Among them were family‐based studies (9), twin studies (2), and studies with unrelated participants (27). Seventeen articles investigated TCF7L2 (7 SNPs), 14 investigated PPARγ (1 SNP), and 8 investigated KCNJ11 (5 SNPs). For all investigated SNPs, at least half of the reports indicated no statistically significant association with postprandial insulin AUC. Conclusion: No evidence was found for associations between TCF7L2, PPARγ, and KCNJ11 genotypes and insulin AUC after an OGTT. Future studies should investigate the effect of genetic risk scores on postprandial insulin.