Interactive associations of the INAFM2 rs67839313 variant and egg consumption with type 2 diabetes mellitus and fasting blood glucose in a Chinese population: A family-based study

Background: INAFM2 rs67839313 was associated with type 2 diabetes (T2DM) in Japanese populations but not in other populations. We aimed to validate the association of rs67839313 with T2DM and explore interactive associations of INAFM2 rs67839313 and egg consumption with T2DM and fasting blood glucose (FBG) in a Chinese population.

Methods: In total, 7175 participants (4202 T2DM cases) from 3980 families were included and categorized into two groups (<4 and ≥4 eggs/week) according to the median egg consumption. Multilevel logistic regression and linear regression models were performed to estimate the genetic associations of rs67839313 with T2DM and FBG, respectively. The crossproduct term between the variant and egg was included in the models for interaction analysis.

Results: We found that rs67839313_T was associated with an increased risk of T2DM (1.22 [95% CI: 1.17-1.27], P < 0.001). Among individuals with the rs67839313_T genotype, those with egg consumption <4/week (1.37 [1.25-1.51]) had a higher T2DM risk than those with egg consumption ≥4/week (1.17 [1.11-1.23]). A significant interactive effect between rs67839313_T and egg consumption on T2DM risk was identified (P = 0.008). Moreover, among participants without T2DM, rs67839313_T was associated with FBG, with a 0.188 mmol/l increase and a 0.152 mmol/l decrease among those consuming <4 eggs/week and ≥4 eggs/week, respectively. The interaction between rs67839313_T and egg consumption was observed to be significantly associated with FBG (P = 0.003).

Conclusions: INAFM2 rs67839313_T was associated with increased T2DM risk and FBG levels in Chinese individuals, and consuming more eggs may eliminate the associated genetic risk. This finding has important implications for understanding the genetic pathogenesis of T2DM and for the precision nutrition management of T2DM.