Association of the SLC22A1, SLC22A2, and SLC22A3 genes encoding organic cation transporters with diabetic nephropathy and hypertension

Riitta Sallinen, Mari A. Kaunisto, Carol Forsblom, Merlin Thomas, Johan Fagerudd, Kim Pettersson-Fernholm, Per Henrik Groop, Maija Wessman, on behalf of the Finnish Diabetic Nephropathy Study Group

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12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)296-304
Number of pages9
JournalAnnals of Medicine
Volume42
Issue number4
DOIs
Publication statusPublished - 1 Jan 2010
Externally publishedYes

Keywords

  • Diabetes mellitus type 1
  • Diabetic nephropathy
  • Genetic association analysis
  • Hypertension
  • Organic cation transporters
  • Single nucleotide polymorphism
  • SLC22A1
  • SLC22A2
  • SLC22A3

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