Diabetes/hyperglycemia risk loci linked with lipoprotein traits
MedWire News: Several genetic risk loci for Type 2 diabetes and hyperglycemia are also associated with lipoprotein traits, an international research team has shown.
Markku Laakso (University of Eastern Finland, Kuopio) and team investigated the effects of 34 genetic risk variants for hyperglycemia/Type 2 diabetes on lipoprotein subclasses and particle composition in a large population-based cohort.
The subjects were 6580 nondiabetic men from the Metabolic Syndrome in Men (METSIM) study, who were genotyped for 34 single nucleotide polymorphisms (SNPs), comprising 20 risk SNPs for diabetes and 14 risk SNPs for fasting and 2-hour glucose.
Writing in the journal Diabetes, Laakso et al reveal that four of the SNPs were significantly associated with lipoprotein traits, after adjustment for confounders and correction for multiple testing.
Specifically, the glucose-raising rs780094 variant of the GCKR gene was significantly associated with low concentrations of very-low-density lipoprotein (VLDL) particles and small low-density lipoprotein (LDL). This variant was also nominally associated with low concentrations of intermediate-density lipoprotein and all LDL subclasses, and with high concentrations of very large and large high-density lipoprotein (HDL) particles.
The glucose-raising rs174550 variant of FADS1 was significantly associated with high concentrations of very large and large HDL particles and nominally associated with low concentrations of all VLDL particles.
Finally, rs10923931 in NOTCH2 and rs757210 in HNF1B genes showed nominal or significant associations with several lipoprotein subclasses.
Interestingly, however, a cumulative "genetic risk score" combining all 34 SNPs was not significantly associated with any of the lipoprotein traits. This suggests that there is no overlap between the genetic basis of Type 2 diabetes/hyperglycemia and lipoprotein metabolism, say the authors.
By contrast, there appears to be "some overlap" between the genes affecting both glucose and lipoprotein metabolism.
They conclude: "Only a limited number of risk loci for hyperglycemia/Type 2 diabetes significantly affect lipoprotein metabolism."
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By Joanna Lyford