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01.10.2006 | Article

Association between variants in the genes for adiponectin and its receptors with insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans

verfasst von: D. K. Richardson, J. Schneider, M. J. Fourcaudot, L. M. Rodriguez, R. Arya, T. D. Dyer, L. Almasy, J. Blangero, M. P. Stern, R. A. DeFronzo, R. Duggirala, C. P. Jenkinson

Erschienen in: Diabetologia | Ausgabe 10/2006

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Abstract

Aims/hypothesis

The aim of this study was to examine whether genetic variation in ADIPOQ, ADIPOR1 and ADIPOR2 may contribute to increased susceptibility to components of the insulin resistance syndrome (IRS).

Materials and methods

We genotyped single-nucleotide polymorphisms (SNPs) in ADIPOQ, ADIPOR1 and ADIPOR2 in Mexican American subjects (N=439) and performed an association analysis of IRS-related traits.

Results

Of the eight SNPs examined in the ADIPOQ gene, rs4632532 and rs182052 exhibited significant associations with BMI (p=0.029 and p=0.032), fasting specific insulin (p=0.023 and p=0.026), sum of skin folds (SS) (p=0.0089 and p=0.0084) and homeostasis model assessment of insulin sensitivity (HOMA-%S) (p=0.015 and p=0.016). Two other SNPs, rs266729 and rs2241767, were significantly associated with SS (p=0.036 and p=0.013). SNP rs7539542 of ADIPOR1 was significantly associated with BMI, SS and waist circumference (p=0.025, p=0.047 and p=0.0062). Fourteen of the ADIPOR2 SNPs were found to be significantly (p<0.05) associated with fasting plasma triglyceride concentrations. Four of these SNPs (rs10848569, rs929434, rs3809266 and rs12342) were in high pairwise linkage disequilibrium (r ²=0.99) and were strongly associated with fasting triglyceride levels (p=0.00029, p=0.00016, p=0.00027 and p=0.00021). Adjusting for the effects of BMI and HOMA-%S on triglyceride concentrations increased significance to p=0.000060 for SNP rs929434. Bayesian quantitative trait nucleotide analysis was used to examine all possible models of gene action. Again, SNP rs929434 provided the strongest statistical evidence of an effect on triglyceride concentrations.

Conclusions/interpretation

These results provide evidence for association of SNPs in ADIPOQ and its receptors with multiple IRS-related phenotypes. Specifically, several genetic variants in ADIPOR2 were strongly associated with decreased triglyceride levels.

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Titel: Association between variants in the genes for adiponectin and its receptors with insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans
verfasst von: D. K. Richardson
J. Schneider
M. J. Fourcaudot
L. M. Rodriguez
R. Arya
T. D. Dyer
L. Almasy
J. Blangero
M. P. Stern
R. A. DeFronzo
R. Duggirala
C. P. Jenkinson
Publikationsdatum: 01.10.2006
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 10/2006
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-006-0384-3

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Abstract

Aims/hypothesis

Materials and methods

Results

Conclusions/interpretation

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