Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes with and without diabetic nephropathy.
OBJECTIVE
Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is the most abundant adipose-specific protein. It is beneficial in that it improves insulin sensitivity and mitigates vascular damage, in addition to the possibility of it having anti-inflammatory properties. Clinical evidences demonstrate that serum adiponectin concentrations are increased in patients with type 1 diabetes (T1D) as well as in patients with microvascular complications. However, the genetic influence of the ACDC gene in T1D and diabetic microvascular complications is still unclear. The present study aims to evaluate the association of the ACDC genetic variation in T1D and diabetic nephropathy (DN).


METHODS
Ten single nucleotide polymorphisms (SNPs) of the ACDC gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187 nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic allele specific hybridization.


RESULTS
Single-marker association analysis demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further analysis for haplotypes of these two SNPs indicated that one of the common haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430-2.188)]. However, there was no significant difference in the allele frequencies of these two SNPs between the groups of T1D patients with nephropathy and the patients without nephropathy.


CONCLUSIONS
The present study thus suggests that SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not with DN among Swedish Caucasians.
Ma
Jun
J
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Möllsten
Anna
A
Falhammar
Henrik
H
Brismar
Kerstin
K
Dahlquist
Gisela
G
Efendic
Suad
S
Gu
Harvest F
HF
D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D013548:Sweden; D044465:White People
D052242:Adiponectin; D004247:DNA