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04-01-2010 | Cardiometabolic | Article

INSIG2 gene variants linked to age-related decline in HDL cholesterol


Free abstract

MedWire News: Two single nucleotide polymorphisms (SNPs) of the insulin-induced gene 2 (INSIG2) are associated with age-related decline in high-density lipoprotein (HDL) cholesterol, report researchers.

The rs7566605 SNP located upstream of INSIG2 has previously been associated with obesity, as reported by MedWire News, although other results have been conflicting.

In this study, Myriam Fornage (University of Texas Health Science Center at Houston, USA) and colleagues genotyped 4304 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study for 12 SNPS located in or near INSIG2 including rs7566605. The cohort comprised 49.5% Black and 50.5% White individuals, who were aged 25 years on average at baseline.

The investigators tested for associations between these 12 SNPs and body mass index (BMI), waist circumference, and measures of lipid metabolism. Interaction of the SNPs with age over 20 years of follow-up was also assessed by the researchers.

Fornage and team found that, although rs7566605 was not associated with variation in lipids or body size at any age, two other SNPs – rs1352083 and rs10185316 – were significantly associated with age-related decline in HDL cholesterol in White individuals.

For example, White participants carrying the risk associated G allele of rs10185316 had 0.84 mg/dl (0.02 mmol/l) lower HDL cholesterol levels per copy at baseline than non-carriers. After 20 years of follow-up, levels were 1.8 mg/dl (0.04 mmol/l) lower in carriers than non-carriers. A similar trend was seen for the risk associated T allele of rs1352083.

Among Black participants, these SNPS were only associated with an age-related decline in HDL cholesterol in those with a BMI below 25 kg/m2.

“The molecular mechanisms that mediate these relationships remain to be investigated,” write the authors.

They conclude: “In particular, characterization of functional variants in the INSIG2 gene will contribute toward a better understanding of the role of this gene in susceptibility to metabolic and cardiovascular dysfunction.”

The results of this study are published in the journal Metabolism: Clinical and Experimental.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Helen Albert