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Genetic variation in PPARG, TCF7L2, and FTO are associated with plasma calcium, fasting glucose and obesity in an island population of the eastern Adriatic (CROSBI ID 555898)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija

Karns, R. A. ; Zhang, G. ; Jeran, Nina ; Havaš Auguštin, Dubravka ; Missoni, Saša ; Sun, G. ; Cheng, H. ; Indugula, S.R. ; Mallik, J. ; Durakovic, Zijad et al. Genetic variation in PPARG, TCF7L2, and FTO are associated with plasma calcium, fasting glucose and obesity in an island population of the eastern Adriatic // The 59th Annual Meeting of The American Society of Human Genetics / / (ur.). 2009. str. /-/

Podaci o odgovornosti

Karns, R. A. ; Zhang, G. ; Jeran, Nina ; Havaš Auguštin, Dubravka ; Missoni, Saša ; Sun, G. ; Cheng, H. ; Indugula, S.R. ; Mallik, J. ; Durakovic, Zijad ; Chakraborty, Ranajit ; Rudan, Pavao ; Deka, Ranjan.

engleski

Genetic variation in PPARG, TCF7L2, and FTO are associated with plasma calcium, fasting glucose and obesity in an island population of the eastern Adriatic

We performed an association analysis of 97 Single Nucleotide Polymorphisms (SNPs) in eight candidate genes (FTO, INSIG2, PPARG, MC4R, SLC30A8, CDKN2A, TCF7L2 and HHEX) with 17 metabolic traits in a sample of >950 unrelated adult individuals from the island of Hvar in the eastern Adriatic coast of Croatia. This population of Slavic origins, living in relative isolation for over 400 years, has a high prevalence (~26%) of metabolic syndrome despite maintaining traditional life style patterns and adherence to a Mediterranean diet. The traits include anthropometric, blood pressure measurements, fasting plasma glucose, insulin, total cholesterol, HDL-C, LDL-C, triglyceride, uric acid, calcium, creatinine, fibrinogen and HbA1c levels. SNPs were either selected from published GWAS (SNPs with genome-wide significance in FTO, INSIG2, MC4R, SLC30A8, CDKN2A, TCF7L2, and HHEX) or tagSNPs (FTO, INSIG2, and PPARG). Three SNPs maintain significance after permutation tests and Bonferroni adjustments (p values reported here are permutation p-values multiplied by the number of traits). Two SNPs in TCF7L2, rs7903146 and rs1225536, are significantly associated with fasting plasma glucose (p=.0042 and p=.0069, respectively) and HbA1c (p=.0031 and p=.0046, respectively). These results are consistent with previous findings that variants in TCF7L2 influence Type 2 diabetes related phenotypes. Our most important finding is an association between plasma calcium concentration and rs1152005, a tagging SNP downstream of PPARG (p=.011). Calcium dysregulation in platelets, reported in patients with diabetes, causes hyperactivity and increased aggregation of platelets. While variants in PPARG have been implicated in the development of obesity and diabetes, to our knowledge, this is the first reported association between a variant in or near PPARG and plasma calcium concentration. Eight SNPs, including five previously reported with genome-wide significance, within a 45Kb region in FTO show nominal significance with BMI and waist circumference. Although their significance do not hold after multiple test adjustments, the FTO region needs further investigation given the gene being strongly implicated in obesity related traits.

metabolic syndrome; gene association studies; plasma calcium; diabetes; obesity; island isolate

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Podaci o prilogu

/-/.

2009.

objavljeno

Podaci o matičnoj publikaciji

The 59th Annual Meeting of The American Society of Human Genetics

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Podaci o skupu

The 59th Annual Meeting of The American Society of Human Genetics, Honolulu, USA, 2009.

poster

20.10.2009-24.10.2009

Honolulu (HI), Sjedinjene Američke Države

Povezanost rada

Temeljne medicinske znanosti, Etnologija i antropologija