Association of sequence variations in the gene encoding insulin-like growth factor binding protein 5 with adiponectin.
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.
Kallio
P
P
Department of Clinical Nutrition, Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland. petteri.kallio@uku.fi
Tolppanen
A-M
AM
Kolehmainen
M
M
Poutanen
K
K
Lindström
J
J
Tuomilehto
J
J
Kuulasmaa
T
T
Kuusisto
J
J
Pulkkinen
L
L
Uusitupa
M
M
D052242:Adiponectin / Q000378:metabolism*; D015992:Body Mass Index; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050151:Subcutaneous Fat / Q000378:metabolism
D052242:Adiponectin; D018975:Insulin-Like Growth Factor Binding Protein 5