The role of vitamin D is difficult to ascertain in short intervention studies as the development of CVD is slow and may begin already in childhood ( Reference Li, Chen and Srinivasan15– Reference Chen and Wang19). Many observational studies show that low vitamin D status is associated with an unfavourable cardiovascular risk profile in children ( Reference Dolinsky, Armstrong and Mangarelli1– Reference Ekbom and Marcus3) and adults ( Reference Parker, Hashmi and Dutton4– Reference Ke, Mason and Kariuki7), but results on the effect of vitamin D supplementation on cardiometabolic markers are inconsistent ( Reference Ferira, Laing and Hausman8– Reference Wang, Xia and Yang14). However, VDR polymorphisms modified associations with vitamin D, which warrants further investigation of VDR's role in the relationship between vitamin D and cardiometabolic risk. In conclusion, genetic variation affected 25(OH)D substantially, but the genetic score was not associated with cardiometabolic markers in children. However, interactions were indicated for the three VDR SNP ( P interaction < 0♰81) on associations between 25(OH)D and TAG, systolic blood pressure and insulin, which all decreased with increasing 25(OH)D only in major allele homozygotes ( β –0♰2 (95 % CI –0♰4, –0♰1) mmol/l β –0♵ (95 % CI –0♹, –0♱) mmHg and β –0♵ (95 % CI –1♴, 0♳) pmol/l, respectively). A risk score based on four of the six SNP was associated with 3♴ (95 % CI 2♶, 4♲) mmol/l lower 25(OH)D per risk allele ( P < 0♰01), but was not associated with the cardiometabolic markers. All GC and CYP2R1 SNP influenced serum 25(OH)D. Furthermore, we examined whether SNP related to vitamin D actions modified associations between 25(OH)D and the cardiometabolic markers. We generated a genetic risk score based on SNP associated with low 25(OH)D and investigated associations between this and blood pressure, plasma lipids and insulin. In 699 healthy 8–11-year-old children, we genotyped eleven SNP. This Mendelian randomisation study examined associations between cardiometabolic markers in children and SNP in genes related to vitamin D metabolism ( DHCR7 group-specific complement ( GC) cytochrome P450 subfamily IIR1 ( CYP2R1) and CYP24A1) and action ( CYP27B1 and VDR). Observational studies show associations between low serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk markers.
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