(P17-024-24) Body Mass Index Mediates Association of SLC39A8 SNP rs13107325 With Circulating High Density Lipoprotein and Triglyceride Concentrations in a UK Biobank Population Cohort

Objectives: Genome-wide association studies link metal transporter SLC39A8 single nucleotide polymorphism (SNP) rs13107325 with greater body mass index (BMI), reduced high density lipoprotein (HDL), and increased triglyceride (Trig) concentrations. We investigated the association of rs13107325 with BMI and circulating HDL and Trig concentrations and whether BMI mediated the effects of rs13107325 on serum HDL and Trig concentrations.

Methods: Regressions were carried out in a UK Biobank population cohort with Caucasian genetic background and without other kinship. Primary exposures were rs13107325 genotype and dietary manganese (Mn). Primary outcomes were BMI, HDL, and Trig. Analyses were adjusted for total dietary energy intake, age, sex, income, qualifications, townsend deprivation index (as measure of socioeconomic status), and smoking. Fasting time was included for random lipid blood tests. Associations between exposures and outcomes were analyzed through quantile regression. We investigated the proportion of effect for rs13107325 on HDL and Trig mediated by BMI using casual mediation analysis and non-parametric bootstrapping (10,000 simulations) following linear regression. Significance was set at p< 0.05.

Results: SNP rs13107325 (beta=0.0249±0.0402, mean±SE, p-value=5.97E-10, N=107,966) and lower dietary Mn intake (beta=-0.543±0.0120, p-value= < 1E-300) was associated with higher BMI. HDL levels were reduced with rs13107325 (beta=-0.0307±0.00375, p-value= 2.99E-16, N=95,318) and lower dietary Mn intake (beta=0.0069±0.00112, p-value= 1.06E-09). Significant associations were found between total Trig and rs13107325 (beta=0.0307±0.00764, p-value=6E-5, N=104,161) and dietary Mn (beta=-0.0428±0.00228, p-value=2.52E-78). Mediation analysis showed that 27% (95% confidence interval/CI 22%-35%, p-value= < 0.0001, N=93,842) of the effect of rs13107325 on HDL was mediated by BMI. For Trig, 58% (95% CI 41-89%, p-value= < 0.0001, N=93,842) of the effect of rs13107325 on Trig was mediated through BMI.

Conclusions: More rs13107325 alleles and lower dietary Mn are associated with higher BMI, decreased HDL, and increased Trig. BMI partially mediates the associations between rs13107325 and serum HDL and Trig concentrations.

Funding Sources: American Heart Association