INSIG2 gene variant influences lipid, lipoprotein levels
MedWire News: Polymorphisms in the INSIG2 gene have a direct influence on lipid and lipoprotein metabolism, a genetic mapping study has found.
However, the study failed to replicate a previously reported association between INSIG2 variants and body mass index (BMI) and obesity.
James Engert (McGill University, Montreal, Quebec, Canada) conducted a fine-mapping study of single nucleotide polymorphisms (SNPs) spanning over 100 kilobases of the insulin-induced gene 2 (INSIG2) locus.
In total, 18,434 base pairs were sequenced, yielding 32 novel SNPs that were then genotyped in 645 French-Canadian individuals in the Quebec Family Study.
Reporting their findings in Circulation and Cardiovascular Genetics, Engert et al reveal that two SNPs - rs10490626 and rs12464355 - were associated with levels of both low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. There was no association between these SNPs and BMI, however.
The researchers then sought to replicate their findings in 758 Canadian, 3247 European, and 1695 South Asian individuals.
The significant associations between rs10490626 and both LDL cholesterol and apoB were replicated in all three cohorts.
Moreover, a SNP in the SORBS1 gene, which is involved in insulin-receptor-mediated signalling, was found to be significantly associated with INSIG2 messenger RNA levels and to act in combination with rs10490626 to influence LDL cholesterol levels in each of the three validation cohorts.
Engert et al say that the "consistent effect" observed with both plasma lipid and lipoprotein traits "suggests that INSIG2 may play a much more important role in lipid metabolism than in obesity."
They write: "Further research is needed to determine the functional role of this SNP and its possible differential response to diet."
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By Joanna Lyford