title: KCNQ1 gene variants and risk of new-onset diabetes in tacrolimus-treated renal-transplanted patients.
abstract: Recent genome-wide association studies identified single-nucleotide polymorphisms (SNPs) in the gene encoding the pore-forming subunit of the voltage-gated K+ channel (KCNQ1) as a risk factor for type 2 diabetes. Tacrolimus (Tac) increased the risk of new-onset diabetes after transplantation (NODAT). The aim of this study was to analyze the association between KCNQ1 variants and the risk for NODAT in kidney-transplanted patients who received Tac as primary immunosuppressor. We genotyped three common KCNQ1 SNPs in 145 Spanish patients who received a cadaveric kidney graft and developed NODAT in the first-year post-transplant (the NODAT group), and 260 patients who remained non-diabetics (non-NODAT). In addition, we searched for DNA variants in the whole KCNQ1 coding exons in these patients. SNP rs2237895 (genotype CC) was associated with an increased risk for NODAT in our population (p = 0.008; OR = 1.83, 95% CI = 1.14-2.93), independently of other risk factors as body mass index, recipient age, or tacrolimus dosage. Other KCNQ1 variants were not associated with NODAT in our patients. Our work supported a role for KCNQ1 gene variants as determinants of the risk of developing NODAT among Tac-treated patients.
authors.affiliation: Genética Molecular, Hospital Universitario Central de Asturias, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tavira
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz-Corte
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.forename: Armando
authors.initials: A
authors.lastname: Torres
authors.forename: Juan M
authors.initials: JM
authors.lastname: Díaz
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.forename: Jose M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
mesh_terms: D000328:Adult; D017668:Age of Onset; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D016559:Tacrolimus