Association between Genotype and the Glycemic Response to an Oral Glucose Tolerance Test: A Systematic Review

The inter-individual variability of metabolic response to foods may be partly due to genetic variation. This systematic review aims to assess the associations between genetic variants and glucose response to an oral glucose tolerance test (OGTT). Three databases (PubMed, Web of Science, Embase) were searched for keywords in the field of genetics, OGTT, and metabolic response (PROSPERO: CRD42021231203). Inclusion criteria were available data on single nucleotide polymorphisms (SNPs) and glucose area under the curve (gAUC) in a healthy study cohort. In total, 33,219 records were identified, of which 139 reports met the inclusion criteria. This narrative synthesis focused on 49 reports describing gene loci for which several reports were available. An association between SNPs and the gAUC was described for 13 gene loci with 53 different SNPs. Three gene loci were mostly investigated: transcription factor 7 like 2 (TCF7L2), peroxisome proliferator-activated receptor gamma (PPARγ), and potassium inwardly rectifying channel subfamily J member 11 (KCNJ11). In most reports, the associations were not significant or single findings were not replicated. No robust evidence for an association between SNPs and gAUC after an OGTT in healthy persons was found across the identified studies. Future studies should investigate the effect of polygenic risk scores on postprandial glucose levels.