A single nucleotide polymorphism alters the sequence of SP1 binding site in the adiponectin promoter region and is associated with diabetic nephropathy among type 1 diabetic patients in the Genetics of Kidneys in Diabetes Study.
OBJECTIVE
The adiponectin promoter single nucleotide polymorphism (SNP) -11391G/A is found to be associated with nephropathy in type 1 diabetic (T1D) patients among Danish, but not French, Finnish, and Swedish populations. In the present study, we identified the binding sites for transcriptional factors in the adiponectin promoter region and also evaluated the association between adiponectin promoter polymorphisms and diabetic nephropathy (DN) in T1D patients.


METHODS
Three adiponectin promoter SNPs, including -11377C/G, -11391G/A, and -11426A/G, were genotyped with dynamic allele-specific hybridization. The subjects included 1177 American T1D patients (622 females/555 males) with or without DN. All patients are of European descent and selected from the Genetics of Kidneys in Diabetes (GoKinD) study.


RESULTS
We identified four binding sites of transcriptional stimulatory protein (SP1) in the adiponectin putative promoter and found that the G allele of SNP -11377C/G altered the sequence for one of the SP1 binding sites. This polymorphism was significantly associated with DN in female T1D patients (P=.022, OR=1.352, 95% CI=1.044-1.752). Further analyses indicated the common diplotype (haplotypic genotype) H1/H1, constructed with SNPs -11377C/G and -11391G/A, was significantly associated with DN in females (P=.013), while the association of another diplotype H1/H2 with DN in females was of borderline significance (P=.071).


CONCLUSIONS
The present study thus provides the first evidence that SNP -11377C/G alters the sequence in one of the SP1 binding sites in the adiponectin promoter region. This polymorphism, together with another promoter SNP -11391G/A, may confer susceptibility to the development of DN in T1D patients among the GoKinD population.
Zhang
Dongying
D
Department of Molecular Medicine and Surgery, Rolf Luft Center for Diabetes Research, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Ma
Jun
J
Brismar
Kerstin
K
Efendic
Suad
S
Gu
Harvest F
HF
D000328:Adult; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D003718:Denmark; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D054419:Receptors, Adiponectin / Q000235:genetics*
D007136:Immunoglobulins; D054419:Receptors, Adiponectin; C090698:SP1 antigen