A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans.

Freedman, Barry I; Hicks, Pamela J; Sale, Michele M; Pierson, Eric D; Langefeld, Carl D; Rich, Stephen S; Xu, Jianzhao; McDonough, Caitrin; Janssen, Bart; Yard, Benito A; van der Woude, Fokko J; Bowden, Donald W

Freedman, Barry I; Hicks, Pamela J; Sale, Michele M; Pierson, Eric D; Langefeld, Carl D; Rich, Stephen S; Xu, Jianzhao; McDonough, Caitrin; Janssen, Bart; Yard, Benito A; van der Woude, Fokko J; Bowden, Donald W.

Afiliación

Freedman BI; Department of Internal Medicine, Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA. bfreedma@wfubmc.edu

Nephrol Dial Transplant ; 22(4): 1131-5, 2007 Apr.

Article en En | MEDLINE | ID: mdl-17205963

RESUMEN

BACKGROUND: Four linkage analyses have identified a region on chromosome 18q22-23 that appears to harbour a diabetic nephropathy (DN) susceptibility locus. A trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs. METHODS: We evaluated the role of the CNDP1 5 leucine/5 leucine (5-5) polymorphism (CNDP1 Mannheim) in diabetic end-stage renal disease (ESRD) susceptibility in 858 European Americans: 294 with type 2 DN-associated ESRD (DN-ESRD), 258 with diabetes mellitus (DM) lacking nephropathy and 306 healthy controls. RESULTS: Subjects with DM lacking nephropathy were significantly more likely to be homozygous for the 5-leucine repeat CNDP1 genotype (5-5), compared with those with DN-ESRD (P=0.02). Healthy controls were also more likely to be homozygous for the 5-5 genotype, compared with those with DN-ESRD (P=0.008). No significant difference in 5-5 genotype frequency was observed between healthy controls and DM cases without nephropathy (P=0.74). CONCLUSION: European Americans homozygous for the 5-5 leucine repeat polymorphism in the CNDP1 gene are at significantly reduced risk for developing diabetic ESRD. This replicates the CNDP1 gene association with DN that was initially detected in European Caucasians and in Arabs, and further demonstrates that the CNDP1 gene and carnosine pathway appear to play a role in susceptibility to DN.

Asunto(s)

Nefropatías Diabéticas/etnología; Nefropatías Diabéticas/genética; Dipeptidasas/genética; Fallo Renal Crónico/etnología; Fallo Renal Crónico/genética; Leucina/genética; Repeticiones de Trinucleótidos/genética; Adulto; Anciano; Alelos; Carnosina/fisiología; Estudios de Casos y Controles; Diabetes Mellitus Tipo 2/etnología; Diabetes Mellitus Tipo 2/genética; Europa (Continente)/etnología; Femenino; Ligamiento Genético; Predisposición Genética a la Enfermedad; Genotipo; Humanos; Masculino; Persona de Mediana Edad; Polimorfismo de Nucleótido Simple; Factores de Riesgo; Estados Unidos/epidemiología; Población Blanca/etnología; Población Blanca/genética

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Repeticiones de Trinucleótidos / Nefropatías Diabéticas / Dipeptidasas / Fallo Renal Crónico / Leucina Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: America do norte / Europa Idioma: En Revista: Nephrol Dial Transplant Asunto de la revista: NEFROLOGIA / TRANSPLANTE Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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