Table 1.
Clinical characteristics of the study groups.
Figure 1.
FNDC5 gene locus on human chromosome 1p35.1 and tagging SNPs.
The FNDC5 gene consists of 6 exons and 5 introns and spans 8.47 kb from nucleotide position 33,100,464 to nucleotide position 33,108,934. The analyzed region additionally included 5 kb of the 5′-flanking region and 3 kb of the 3′-flanking region. This genomic region did not overlap with other known gene loci. The locations of the seven common (minor allele frequencies ≥0.05) SNPs in the region and the four tagging SNPs (highlighted by boxes) are indicated by white and black triangles, respectively. HapMap CEU-derived linkage disequilibrium data (r2-values) are presented as shaded diamonds (white – r2 = 0.0; black – r2 = 1.0; grey – in between). CEU – Central Europeans; SNP – single nucleotide polymorphism.
Table 2.
Association of FNDC5 SNPs rs16835198, rs3480, rs726344, and rs1746661 with glycaemia and insulin sensitivity (statistics).
Figure 2.
Association of FNDC5 SNPs rs16835198 and rs726344 with insulin sensitivity.
HOMA-IR (A and C) and ISI OGTT (B and D) data were adjusted for gender, age, and bioelectrical impedance-derived percentage of body fat. Diamonds represent means ±SE. HOMA-IR – homeostasis model assessment of insulin resistance; ISI OGTT – oral glucose tolerance test-derived insulin sensitivity index; SNP – single nucleotide polymorphism.
Figure 3.
Meta-analysis of the effect of FNDC5 SNP rs726344 on insulin sensitivity in TÜF and MAGIC.
The effects of the minor A-allele of SNP rs726344 on fasting insulin (A) and HOMA-IR (B), as derived from multiple linear regression analysis with gender, age, and BMI as confounding variables, were subjected to inverse variance weighted meta-analysis. Effect sizes, 95% confidence intervals, weights, sample sizes, and heterogeneity data are given. HOMA-IR – homeostasis model assessment of insulin resistance; MAGIC – Meta-Analyses of Glucose and Insulin-related traits Consortium; SNP – single nucleotide polymorphism; TÜF – overall study group derived from the Tübingen Family study for type 2 diabetes.
Figure 4.
Association of human myotube FNDC5 mRNA expression with PPARGC1A mRNA expression in vitro and donors’ insulin sensitivity in vivo.
The association between human myotube FNDC5 and PPARGC1A mRNA contents (A) was assessed using simple linear regression analysis. The association between human myotube FNDC5 mRNA expression and fasting insulin levels (B), HOMA-IR (C), ISI OGTT (D), and 2-h plasma glucose levels (E) of 37 young healthy donors recruited in Tübingen and with fasting insulin levels (F) of 14 elderly men recruited in Stockholm was tested by multiple linear regression analysis with gender, age, and bioelectrical impedance-derived percentage of body fat (Tübingen volunteers) or with BMI (Stockholm volunteers) as confounding variables (leverage plots shown). Dotted lines indicate the 95% confidence interval of the regression. HOMA-IR – homeostasis model assessment of insulin resistance.