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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-08-0426v1 159/5/577    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Johansson, L. Articles by Ridderstrale, M. PubMed PubMed Citation Articles by Johansson, L. Articles by Ridderstrale, M.

Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity

L Johansson, Clinical Sciences Malmo, Clinical Obesity, Lund University, Malmo, Sweden
U Lindblad, Clinical Sciences Malmö, Community Medicin, Lund University, Malmö, Sweden
C Larsson, Clinical Sciences Malmo, Community Medicin, Lund University, Malmo, Sweden
L Rastam, Clinical Sciences Malmo, Community Medicin, Lund University, Malmo, Sweden
M Ridderstrale, Clinical Sciences Malmo, Clinical Obesity, Lund University, Malmo, Sweden

Correspondence: Lovisa Johansson, Email: lovisa.johansson{at}med.lu.se

Abstract

Objective: The insulin responsive adiponutrin (PNPLA3 or ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity, and to investigate their effect on insulin resistance and β-cell function.

Methods: rs738409 (Met148Ile) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay in a Swedish population-based sample (n=1811).

Results: Both variant alleles were associated with decreased prevalence of obesity (p<0.05); OR 0.75 [0.61-0.93] per carried Ile-allele for rs738409 and 0.80 [0.64-1.00] per carried G-allele for rs2072907. As a quantitative trait, there was no association in the whole population, but in obese subjects BMI (p=0.023) and waist (p=0.0098) was higher in carriers of the Ile-allele. They also displayed decreased insulin secretion in response to oral glucose tolerance test (30 minutes insulin; p=0.007, insulinogenic index; p=0.0051) with no significant difference in fasting plasma glucose (p=0.31), β-cell function (disposition index; p=0.17) or insulin resistance (HOMA-IR; p=0.063). The correlation between BMI and HOMA-IR differed (Met/X vs. Ile/Ile, p=0.028), Met-allele carriers seemingly more insulin resistant at a lower BMI. The rs2072907 variant show similar results for insulin secretion. The findings were independent of age, gender and level of self reported leisure time physical activity.

Conclusion: We confirm the association between PNPLA3 and obesity. In addition, the rs738409 variant was associated with insulin secretion. There seem to be a differential effect of the Ile-allele depending on the degree of obesity, possibly as a consequence of insulin resistance.