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

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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 beta-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), beta-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.

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  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)577-583
JournalEuropean Journal of Endocrinology
Volume159
Issue number5
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes

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