Metal Transporter Gene SLC39A8 Polymorphism rs13107325 and Dietary Manganese Intake Are Associated with Measures of Cardiovascular Disease Risk in a UK Biobank Population Cohort

<b>Background/Objectives:</b> Metal transporter gene <i>SLC39A8</i> and single nucleotide polymorphism (SNP) rs13107325 are associated with risk factors for atherosclerosis and cardiovascular disease (CVD). However, it is unclear how dietary manganese intake impacts CVD risk factors. The aim of this study was to use the UK Biobank population cohort (276,436 participants, Caucasian genetic ancestry, no genetic kinship) to investigate whether rs13107325 and dietary manganese are associated with CVD risk. <b>Methods:</b> A cross-sectional design and quantile (median) regression was used to determine associations of rs13107325 and dietary manganese intake with indicators of CVD risk. <b>Results:</b> SNP rs13107325 was associated with CVD risk factors, including greater body mass index (BMI) (beta ± SE per rs13107325 allele = 0.283 ± 0.0392, false discovery rate (FDR) < 10^-10) and triglycerides (beta ± SE = 0.0308 ± 0.00761, FDR < 0.001) and reduced high density lipoprotein (HDL) (beta ± SE = -0.0298 ± 0.00343, FDR < 10^-15). SNP rs13107325 was also associated with lower systolic (beta ± SE = -0.601 ± 0.172, FDR < 10^-3) and diastolic blood pressure (beta ± SE = -0.531 ± 0.100, FDR < 10^-5). Dietary manganese intake was positively correlated with measures of favorable cardiovascular health, such as lower BMI (beta ± SE per mg dietary manganese = -0.531 ± 0.0118, FDR < 10^-300), reduced triglycerides (beta ± SE = -0.0451 ± 0.00229, FDR < 10^-50), increased HDL (beta ± SE = 0.00958 ± 0.00103, FDR < 10^-15), and lower blood pressure (systolic beta ± SE = -0.529 ± 0.0520, FDR < 10^-20; diastolic beta ± SE = -0.562 ± 0.0302, FDR < 10^-50). <b>Conclusions:</b> The favorable associations of dietary manganese opposed many deleterious trends associated with rs13107325. Increased dietary manganese may promote cardiovascular health and offset many risks to cardiovascular health linked to SNP rs13107325.