TY - JOUR
T1 - Association of the SLC22A1, SLC22A2, and SLC22A3 genes encoding organic cation transporters with diabetic nephropathy and hypertension
AU - Sallinen, Riitta
AU - Kaunisto, Mari A.
AU - Forsblom, Carol
AU - Thomas, Merlin
AU - Fagerudd, Johan
AU - Pettersson-Fernholm, Kim
AU - Groop, Per Henrik
AU - Wessman, Maija
AU - on behalf of the Finnish Diabetic Nephropathy Study Group
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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. Aims. 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. Subjects and methods. We selected 90 SNPs (≈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.
AB - 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. Aims. 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. Subjects and methods. We selected 90 SNPs (≈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.
KW - Diabetes mellitus type 1
KW - Diabetic nephropathy
KW - Genetic association analysis
KW - Hypertension
KW - Organic cation transporters
KW - Single nucleotide polymorphism
KW - SLC22A1
KW - SLC22A2
KW - SLC22A3
UR - http://www.scopus.com/inward/record.url?scp=77952218666&partnerID=8YFLogxK
U2 - 10.3109/07853891003777109
DO - 10.3109/07853891003777109
M3 - Article
AN - SCOPUS:77952218666
SN - 0785-3890
VL - 42
SP - 296
EP - 304
JO - Annals of Medicine
JF - Annals of Medicine
IS - 4
ER -