Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study.
OBJECTIVE
Adiponectin is a circulating peptide derived from adipose tissue. It mediates its insulin-sensitising and anti-atherogenic effects on target tissues through two known receptors, adiponectin receptors 1 and 2 (ADIPOR1; ADIPOR2), which are encoded by the genes ADIPOR1 and ADIPOR2. Our aim was to study the association of ADIPOR1 gene variations with body size and risk of type 2 diabetes in subjects with impaired glucose tolerance, who participated in the Finnish Diabetes Prevention Study (DPS).


METHODS
We selected seven single nucleotide polymorphisms (SNPs) of the ADIPOR1 gene to perform association studies with anthropometrics and metabolic parameters at baseline, and with the risk of type 2 diabetes during the 3-year follow-up in the DPS study population. Both single SNP analysis and haplotype effects were studied.


RESULTS
Three out of seven markers studied (rs10920534, rs22757538 and rs1342387) were significantly associated with various body size measurements including weight, height, waist and hip circumference, sagittal diameter and body mass index. Furthermore, three markers (rs10920534, rs12045862 and rs7539542), of which two were different from those associating with body size, were linked to fasting and 2-h insulin levels, particularly in men at baseline. The haplotype analysis with five markers revealed seven major haplotypes in the DPS study population. The haplotype effects on body size measures were in line with those of single SNP analysis. However, none of the markers were associated with the risk of type 2 diabetes.


CONCLUSIONS
Our findings suggest that ADIPOR1 has a putative role in the development of body size, and that traits for central adiposity and insulin resistance may be dissociated from each other.
Siitonen
N
N
Department of Public Health and Clinical Nutrition, Clinical Nutrition, and Food and Health Research Centre, University of Kuopio, Kuopio, Finland.
Pulkkinen
L
L
Mager
U
U
Lindström
J
J
Eriksson
J G
JG
Valle
T T
TT
Hämäläinen
H
H
Ilanne-Parikka
P
P
Keinänen-Kiukaanniemi
S
S
Tuomilehto
J
J
Laakso
M
M
Uusitupa
M
M
D049628:Body Size / Q000235:genetics*; D002874:Chromosome Mapping; D003062:Codon / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics / Q000517:prevention & control*; D005091:Exons; D005260:Female; D005387:Finland; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics*
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D003062:Codon; D005819:Genetic Markers; D007328:Insulin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface