L’analyse combinée de 19 variants de gènes de susceptibilité du DT2 a une faible valeur discriminante pour séparer les sujets ayant une tolérance normale au glucose de ceux ayant un diabète de type 2

Abstract

Aims/hypothesis

The list of validated type 2 diabetes susceptibility variants has recently been expanded from 3 to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying receiver operating characteristics (ROC) to demonstrate the discriminatory value between glucose-tolerant individuals and type 2 diabetes patients in a cross-sectional population of Danes.

Methods

The 19 variants were genotyped in three study populations: the population-based Inter99 study; the ADDITION study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals.

Results

Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI: [0.98–1.11]) to 1.33 (95% CI: [1.22–1.45]). When combining the 19 variants, subgroups with extreme risk profiles showed a threefold difference in the risk of type 2 diabetes (lower 10% carriers with ≤ 15 risk alleles vs upper 10% carriers with ≥ 22 risk alleles, OR: 2.93 (95% CI: [2.38−3.62]; P = 1.6 × 10−25). We calculated the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects.

Conclusions/interpretation

Combined analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value.