Association of the SLC22A1, SLC22A2, and SLC22A3 genes encoding organic cation transporters with diabetic nephropathy and hypertension.
BACKGROUND
Diabetic nephropathy (DN) is a severe long-term complication of diabetes characterized by continuous albuminuria, a relentless decline in renal function, and an increased arterial blood pressure.


OBJECTIVE
Our aim was to find out if single nucleotide polymorphisms (SNPs) within the SLC22A1, SLC22A2, and SLC22A3 genes encoding organic cation transporters (OCTs) associate with DN or hypertension.


METHODS
We selected 90 SNPs ( approximately 1 SNP/4 kb) in and surrounding SLC22A1, SLC22A2, and SLC22A3 using the HapMap data. The SNPs were tested for association with DN and hypertension in 1,086 unrelated Finnish patients with type 1 diabetes mellitus (T1DM). Eight of the SNPs were genotyped in 1,252 additional Finnish patients to verify the findings.


RESULTS
We detected nominal evidence of association (P < 0.05) between the SLC22A2 (SNPs rs653753, rs596881, and rs316019) and SLC22A3 (SNPs rs376563, rs2048327, rs2457576, and rs1567438) genes and DN and hypertension in Finnish men with T1DM. We were not, however, able to replicate the associations, and none of them reached the significance limit adjusted for multiple testing (P < 0.00009).


CONCLUSIONS
There was no clear association between the SLC22A1, SLC22A2, and SLC22A3 genes and DN or hypertension. Although several SLC22A2 and SLC22A3 SNPs indicated association, lack of association was evident after the replication study.
Sallinen
Riitta
R
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland. riitta.sallinen@helsinki.fi
Kaunisto
Mari A
MA
Forsblom
Carol
C
Thomas
Merlin
M
Fagerudd
Johan
J
Pettersson-Fernholm
Kim
K
Groop
Per-Henrik
PH
Wessman
Maija
M
D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D000099254:Organic Cation Transporter 3
D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; D000099254:Organic Cation Transporter 3; C491013:SLC22A2 protein, human