Interactions between multiple serum metals and genetic variants for type 2 diabetes risk: A prospective Chinese...

Type 2 diabetes (T2D) is a disease caused by a combination of genetic and environmental exposures. In addition, there is limited epidemiological evidence on the interaction between metal exposure and genetic risk for T2D. Therefore, we analyzed the interaction effect of serum concentrations of multiple metals and genetic variants on T2D incidence in the general population.

A prospective cohort study with 14 years of follow-up was performed with 4507 participants without noncommunicable diseases at baseline. Twenty-one metals were measured using inductively coupled plasma-mass spectrometry (ICP-MS). T2D-associated single nucleotide polymorphisms (SNPs) identified by Genome-wide association study (GWAS) were also genotyped. The polygenic risk score (PRS) models based on 46 SNPs identified from East Asians was constructed. A Cox regression model was used to explore the associations of serum metals and their interaction effects with PRS on T2D.

Of the 4507 participants, 350 were newly diagnosed with T2D during the 14-year follow-up. After adjusting for covariates, serum vanadium, chromium, manganese, molybdenum, barium and lead levels were significantly associated with decreased T2D risk, while zinc levels were correlated with elevated T2D risk (P < 0.05). Furthermore, zinc, molybdenum, barium and lead showed additive interaction with the PRS derived from 46 SNPs specific for east Asians on T2D.

Significant interaction effects were observed for zinc、molybdenum、barium、lead exposure and PRS. Our findings suggest that people with a high genetic risk of diabetes should pay attention to maintaining appropriate levels of metal.