Daniela Vejrazkova, Martin Hill, Marketa Vankova, Petra Lukasova, Josef Vcelak, Olga Bradnova, Tereza Halkova, Veronika Cirmanova, Katerina Andelova, Hana Krejci and Bela Bendlova
Background: Sex hormone-binding globulin (SHBG) belongs to the factors contributing to the pathophysiology of type 2 diabetes mellitus (T2DM). We determined genotypic frequencies of the single nucleotide polymorphisms (SNPs) rs6259 and rs6257 in T2DM patients, offspring of T2DM patients, gestational diabetics, patients suffering from polycystic ovary syndrome (PCOS), and in healthy adult Czechs. 1687 volunteers entered the study. The aim was to compare genetic constellation between the groups and to study the possible association of the SNPs with biochemical and anthropometric markers of insulin sensitivity.
Methods: TaqMan (LC480, Roche) was used for genotyping, statistical evaluation was carried out using Statgraphics Centurion version XVI and NCSS 2007.
Results: The SNPs distribution was similar between the groups. We found lower SHBG concentrations in diabetics and PCOS patients. The rs6259 SNP was associated with SHBG levels: in the NN carriers, the concentration was significantly higher in comparison with DD and DN. Unexpected results were observed when association of the rs6259 SNP with insulin sensitivity was assessed. In spite of higher SHBG concentration, which is considered to be protective factor, the NN homozygotes exhibited systematically higher stimulated glucose levels during the 3-hour oral glucose tolerance test and lower Cederholm index of insulin sensitivity.
Conclusions: Genetic analysis confirmed the association between rs6259 NN genotype and higher SHBG levels. Furthermore, the NN genotype showed higher stimulated glycemia and lower insulin sensitivity. This observation seems intriguing considering established protective effect of higher SHBG levels in relation to T2DM and should be verified on a larger group of probands.