Background: Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response. Objective: The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS). Methods: DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2±4.5 kg/m 2 , age 55 ± 7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2 ± 3.5 kg/m 2 , age 57.7 ± 7.4 years). Results: Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM. Conclusions: Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.

We have reported that the sequence variation in the tenomodulin (TNMD) gene is associated with the risk of type 2 diabetes (T2DM), central obesity and serum levels of systemic immune mediators in the Finnish Diabetes Prevention Study (DPS), which is a longitudinal lifestyle intervention study on 522 middle-aged persons with impaired glucose tolerance (IGT). The aim of this study was to investigate whether the association with T2DM, observed in the DPS could be replicated in a larger, cross-sectional population-based random sample of 5298 men (3020 with normoglycaemia, 984 with impaired fasting glucose, 436 with IGT and 811 with T2DM) from the region of Kuopio, eastern Finland. To further explore the putative mechanisms linking TNMD to T2DM and metabolic syndrome, we studied the associations of TNMD sequence variation with lipid abnormalities characteristic to metabolic syndrome. The association with T2DM risk was not replicated, but significant associations were found with serum low-density lipoprotein and total cholesterol in a body mass index-dependent manner. These associations were also observed in the men of DPS, whereas in women these associations were not significant. These results from two independent study populations suggest that the genetic variation in TNMD could modulate cholesterol metabolism in obese men.

Purpose: Tenomodulin (TNMD) is located in the X-chromosome encoding a putative angiogenesis inhibitor which is expressed in retina. Associations of single nucleotide polymorphisms of TNMD with the prevalence of age-related macular degeneration (AMD) were examined. Methods: Six markers covering 75% of the common sequence variation in the coding region of TNMD and 10 kb up-and downstream were genotyped in a sample consisting of 89 men and 175 women with exudative AMD, 18 men and 25 women with atrophic AMD, and 55 men and 113 women without AMD. All participants were over 65 years old and did not have diabetes mellitus. Due to the chromosomal locus, the association of genotypes with AMD was assessed genderwise. Results: Three markers, rs1155974, rs2073163, and rs7890586, were associated with a risk of AMD in women. In comparison to women with other genotypes, the women who were homozygous for the minor allele (genotypes rs1155974-TT or rs2073163-CC) had 2.6 fold (p=0.021) or 1.9 fold (p=0.067) risk for having AMD, respectively. These differences were due to the unequal prevalence of exudative AMD. In comparison to women who were homozygous for the major alleles, the women with rs1155974-TT genotype had a 2.8 fold risk (p=0.021 in additive model; p=0.022 in recessive model) for exudative AMD, and the women with rs2073163-CC genotype had a 1.8 fold risk (p=0.09 in additive model; p=0.038 in recessive model). Furthermore, women carrying the rare rs7890586-AA genotype had a significantly smaller risk for having AMD than women with the other genotypes (odds ratio 0.083; p=0.001 in recessive model), but due to the low frequency of this genotype, this finding must be interpreted cautiously. The false discovery rate was <10% for all of the aforementioned results. Conclusions: On the basis of the putative antiangiogenic role of TNMD and the present genetic associations of TNMD with AMD in women, we suggest that TNMD could be a novel candidate gene for AMD. These results should be confirmed in further studies. Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly [1]. It is attributable to degenerative tissue alterations occurring at the interface between the neural retina and underlying choroid [2,3]. AMD can be divided into atrophic and exudative forms. The atrophic form is more common and accounts for approximately 80% of AMD cases. However, the exudative form accounts for the majority of advanced cases [4]. The disease etiology is multifactorial-i.e., in addition to a substantial genetic component [5], aging, smoking, high body mass index, hypertension, and hypercholesterolemia predispose to AMD [6][7][8][9][10][11]. Choroidal neovascularization and