Endocrine Abstracts

Introduction: Hypercholesterolemia is frequently found in patients with type 2 diabetes (T2D). Cholesterol is metabolized from 7-dehydrocholesterol by 7-dehydrocholesterol reductase (DHCR7) from 7-dehydrocholesterol, a precursor of pre-vitamin D3. Therefore single nucleotide polymorphisms (SNP) in the DHCR7 gene could regulate cholesterol levels and concentrations of vitamin D metabolites (25(OH)D₃ or 1,25(OH)₂D₃). For this purpose we investigated the SNP rs12785878 located near the DHCR7 gene in German T2D patients and healthy controls (HC) as well as concentrations of vitamin D metabolites.

Methods: 527 T2D patients and 654 HC were genotyped for the DHCR7 SNP rs12785878 by a Taqman assay. Additionally, 25(OH)D₃ and 1,25(OH)₂D₃ plasma levels of 76 T2D patients and 281 HC were measured by RIA.

Results: The homozygous TT genotype was significantly more frequent in T2D patients compared to HC (TT: 54.9 vs 50.2%; GT: 38.4 vs 37.8%, GG: 6.6 vs 12.1%, P=0.007), also the allele T (74.1 vs 69.0% OR =1.22; 95% CI: 1.02-1.46) in contrast to allele G (25.9 vs 31.0% OR =0.82; 95% CI: 0.68–0.98, P=0.03). T2D patients had significantly lower 25(OH)D₃ (median 12.6 vs 19.4 ng/ml P=0.0001) and 1,25(OH)₂D₃ levels (median 44.7 vs 51 pg/ml P=0.001) compared to HC. T2D patients with DHCR7 genotypes GG and GT had lower 25(OH)D₃ levels than those from HC with genotype GG and GT, and T2D patients with the TT genotype showed even lower 25(OH)D₃ (median 13.7 vs 20.9 ng/ml P=0.002) and 1,25(OH)₂D₃ levels (median 43.3 vs 52.3 pg/ml P=0.001) compared to HC with the same genotype.

Conclusion: Our results reveal an association of the DHCR7 SNP rs12785878 with German T2D patients. The allele T may predispose to the development of T2D. In addition, significantly lower VD levels were observed in T2D patients with the TT genotype. The dysfunction of DHCR7 may contribute to the complex pathophysiology of insulin action and or ß-cell secretion independent from its effect on VD deficiency being a risk factor for T2D development.