title: rs1888747 polymorphism in the FRMD3 gene, gene and protein expression: role in diabetic kidney disease.
abstract: BACKGROUND
  We carried out a case-control study in patients with type 2 diabetes mellitus (T2DM) to evaluate the association between seven single nucleotide polymorphisms (SNPs) previously described to be linked to diabetic kidney disease (DKD) in type 1 diabetes mellitus (T1DM). Additionally, we evaluated gene and protein expression related to the polymorphism associated with DKD.
  
  
  METHODS
  The association study included 1098 T2DM patients (718 with DKD and 380 without DKD). Out of the 13 polymorphisms associated with DKD in a previous study with T1DM, seven were chosen for evaluation in this sample: rs1888747, rs9521445, rs39075, rs451041, rs1041466, rs1411766 and rs6492208. The expression study included 91 patients who underwent nephrectomy. Gene expression was assessed by RT-qPCR and protein expression in kidney samples was quantified by western blot and it localization by immunohistochemistry.
  
  
  RESULTS
  The C/C genotype of rs1888747 SNP was associated with protection for DKD (OR = 0.6, 95 % CI 0.3-0.9; P = 0.022). None of the other SNPs were associated with DKD. rs1888747 is located near FRMD3 gene. Therefore, FRMD3 gene and protein expression were evaluated in human kidney tissue according to rs1888747 genotypes. Gene and protein expression were similar in subjects homozygous for the C allele and in those carrying the G allele.
  
  
  CONCLUSIONS
  Replication of the association between rs1888747 SNP and DKD in a different population suggests that this link is not the result of chance. rs1888747 SNP is located at the FRMD3 gene, which is expressed in human kidney. Therefore, this gene is a candidate gene for DKD. However, in this study, no rs1888747 genotype or specific allele effect on gene and/or protein expression of the FRMD3 gene was demonstrated.
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil ; Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Marjoriê P
authors.initials: MP
authors.lastname: Buffon
authors.affiliation: Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Carpena
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil ; Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Sortica
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Santer
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil ; Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Carlessi
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil ; Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Bianca M
authors.initials: BM
authors.lastname: de Souza
authors.affiliation: Pathology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS Brazil ; Post-Graduation Program in Medical Sciences: Ginecology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Edelweiss
authors.affiliation: Urology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS Brazil.
authors.forename: Milton
authors.initials: M
authors.lastname: Berger
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil ; Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, RS 90035-003 Brazil ; Post-Graduation Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS Brazil.
authors.forename: Luís H
authors.initials: LH
authors.lastname: Canani
keywords: Diabetic kidney disease; FRMD3 gene expression; Human kidney; Polymorphism