TY - JOUR

T1 - Vitamin D-related genes and cardiometabolic markers in healthy children: a Mendelian randomisation study

AU - Lopez-Mayorga, Ania

AU - Hauger, Hanne

AU - Petersen, Rikke A

AU - Vogel, Ulla

AU - Damsgaard, Camilla Trab

AU - Lauritzen, Lotte

N1 - CURIS 2020 NEXS 083 (Embargo)

PY - 2020

Y1 - 2020

N2 - Observational studies in adults and children show associations between low serum 25-hydroxyvitamin D (25(OH)D) and an adverse cardiometabolic risk profile. This Mendelian randomization study examines associations between cardiometabolic markers in children and single nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism and action. In 699 healthy 8-11-year-old children, we genotyped SNPs in vitamin D-related genes (DHCR7 (rs12785878, rs3829251); GC (rs4588, rs7041, rs12512631); CYP2R1 (rs10741657, rs10500804, rs156292); CYP27B1 (rs10877012); CYP24A1 (rs2296241); VDR (rs757343, rs2228570, rs11568820)). We generated a genetic risk score based on SNPs associated with low autumn 25(OH)D and investigated associations between the score and blood pressure, plasma lipids, and insulin. Furthermore, we examined whether SNPs in genes related to mechanisms of action modified associations between 25(OH)D and the cardiometabolic markers. All GC and CYP2R1 SNPs influenced serum 25(OH)D. A risk score based on four of the SNPs was associated with 3.4[95%CI 2.6;4.2] mmol/L lower 25(OH)D per risk allele (P<0.001), but was not associated with any of the cardiometabolic markers. However, VDR SNP-interactions were indicated on associations between 25(OH)D and triacylglycerol, systolic blood pressure, and insulin, which all decreased with increasing 25(OH)D only in major allele homozygotes of rs2228570 (β=-0.02[-0.04;-0.01] mmol/L, Pinteraction=0.021), rs11568820 (β=-0.5[-0.9;-0.1] mmHg, Pinteraction=0.081), and rs757343 (β=-0.5[-1.4;0.3] pmol/L, Pinteraction=0.077), respectively. In conclusion, genetic variation affected 25(OH)D substantially, but was not associated with cardiometabolic markers. However, VDR polymorphisms modified associations between vitamin D and some cardiometabolic markers in children. This warrants further investigation of the role of VDR in the relationship between vitamin D-status and cardiometabolic risk.

AB - Observational studies in adults and children show associations between low serum 25-hydroxyvitamin D (25(OH)D) and an adverse cardiometabolic risk profile. This Mendelian randomization study examines associations between cardiometabolic markers in children and single nucleotide polymorphisms (SNPs) in genes related to vitamin D metabolism and action. In 699 healthy 8-11-year-old children, we genotyped SNPs in vitamin D-related genes (DHCR7 (rs12785878, rs3829251); GC (rs4588, rs7041, rs12512631); CYP2R1 (rs10741657, rs10500804, rs156292); CYP27B1 (rs10877012); CYP24A1 (rs2296241); VDR (rs757343, rs2228570, rs11568820)). We generated a genetic risk score based on SNPs associated with low autumn 25(OH)D and investigated associations between the score and blood pressure, plasma lipids, and insulin. Furthermore, we examined whether SNPs in genes related to mechanisms of action modified associations between 25(OH)D and the cardiometabolic markers. All GC and CYP2R1 SNPs influenced serum 25(OH)D. A risk score based on four of the SNPs was associated with 3.4[95%CI 2.6;4.2] mmol/L lower 25(OH)D per risk allele (P<0.001), but was not associated with any of the cardiometabolic markers. However, VDR SNP-interactions were indicated on associations between 25(OH)D and triacylglycerol, systolic blood pressure, and insulin, which all decreased with increasing 25(OH)D only in major allele homozygotes of rs2228570 (β=-0.02[-0.04;-0.01] mmol/L, Pinteraction=0.021), rs11568820 (β=-0.5[-0.9;-0.1] mmHg, Pinteraction=0.081), and rs757343 (β=-0.5[-1.4;0.3] pmol/L, Pinteraction=0.077), respectively. In conclusion, genetic variation affected 25(OH)D substantially, but was not associated with cardiometabolic markers. However, VDR polymorphisms modified associations between vitamin D and some cardiometabolic markers in children. This warrants further investigation of the role of VDR in the relationship between vitamin D-status and cardiometabolic risk.

KW - Faculty of Science

KW - Vitamin D

KW - Genetic polymorphisms

KW - Children

KW - Cadiometabolic risk

U2 - 10.1017/S0007114520000148

DO - 10.1017/S0007114520000148

M3 - Journal article

C2 - 31959263

VL - 123

SP - 1138

EP - 1147

JO - British Journal of Nutrition

JF - British Journal of Nutrition

SN - 0007-1145

IS - 10

ER -