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Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and predispose to younger age at diagnosis of diabetes |
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| Authors: | Ineta Kalnina Linda Zaharenko Iveta Vaivade Vita Rovite Liene Nikitina-Zake Raitis Peculis Davids Fridmanis Kristine Geldnere Josefin A Jacobsson Markus S Almen Valdis Pirags Helgi B Schiöth Janis Klovins |
| Institution: | 1. Latvian Biomedical Research and Study Centre, Ratsupites Street 1, LV-1067 Riga, Latvia;2. Faculty of Biology, University of Latvia, Kronvalda blvd.4, LV-1586 Riga, Latvia;3. Department of Endocrinology, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, LV1002 Riga, Latvia;4. Faculty of Medicine, University of Latvia, Sarlotes Street 1a, LV1001 Riga, Latvia;5. Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, PO Box 593, 751 24 Uppsala, Sweden |
| Abstract: | Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB). We confirmed association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with T2D. Association between SNP in FTO and T2D remained significant after correction for body mass index (BMI). The rs57103849 located in the fourth intron of FTO and rs7561317 in TMEM18 showed BMI independent association with younger age at diagnosis of T2D. Our results add to the evidence that BMI related variants in and near FTO and TMEM18 may increase the risk for T2D not only through secondary effects of obesity. The influence of variants in the fourth intron of the FTO gene on development of T2D may be mediated by mechanisms other than those manifested by SNPs in the first intron of the same gene. |
| Keywords: | T2D type 2 diabetes SNP single nucleotide polymorphisms BMI body mass index logBMI logarithmically transformed body mass index values FTO the fat mass and obesity associated TMEM18 transmembrane 18 GWA genome wide association LD linkage disequilibrium LGDB Latvian Genome Data Base ICD-10 International Statistical Classification of Diseases 10th Revision OR odds ratio CEU Utah residents with ancestry from northern and western Europe IRX3 iroquois homeobox 3 SD standard deviation CI confidence interval freq frequency n number RAF risk allele frequency p-perm p - values derived performing permutation tests specifying 100000 permutations and corrected for multiple testing (EMP2) EMP2 corrected empirical p-value ns non-significant Add additive Rec recessive |
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