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

Johansson, Lovisa LU ; Lindblad, Ulf LU ; Larsson, Charlotte A LU ; Råstam, Lennart LU and Ridderstråle, Martin LU (2008) In European Journal of Endocrinology 159(5). p.577-583
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Endocrinology
volume
159
issue
5
pages
577 - 583
publisher
Society of the European Journal of Endocrinology
external identifiers
  • wos:000260965600012
  • pmid:18728122
  • scopus:55749101261
ISSN
1479-683X
DOI
10.1530/EJE-08-0426
language
English
LU publication?
yes
id
8bf9017a-b400-4864-8aeb-07324044f177 (old id 1222921)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18728122?dopt=Abstract
date added to LUP
2008-09-03 12:43:43
date last changed
2017-09-17 05:06:47
@article{8bf9017a-b400-4864-8aeb-07324044f177,
  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&lt;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.},
  author       = {Johansson, Lovisa and Lindblad, Ulf and Larsson, Charlotte A and Råstam, Lennart and Ridderstråle, Martin},
  issn         = {1479-683X},
  language     = {eng},
  number       = {5},
  pages        = {577--583},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity.},
  url          = {http://dx.doi.org/10.1530/EJE-08-0426},
  volume       = {159},
  year         = {2008},
}