eNOS gene Glu298Asp and 4b/a polymorphisms are associated with renal function parameters in Mexican patients with Fabry disease.
Fabry disease (FD) is an inherited X-linked lysosomal disease that causes renal failure in a high percentage of affected individuals. The eNOS gene encodes for endothelial nitric oxide synthase, which plays an important role in glomerular hemodynamics. This gene has two main polymorphisms (Glu298Asp and 4b/a) that have been studied in the context of many different diseases, including those involving cardiovascular and renal alterations. Considering the lack of information regarding eNOS variants and FD, we investigated whether there were associations between eNOS genetic variants and renal function parameters in Mexican patients with FD and renal impairment. In total, 15 FD patients with renal alterations were included in the present study, and associations between eNOS polymorphisms and renal function parameters (urea, creatinine, and GFR) were evaluated. The Asp298 and 4a alleles of the eNOS gene were found to be significantly associated with increased levels of urea and creatinine, and a decreased glomerular filtration rate in FD patients, and this association behaved in a co-dominant fashion. Our results coincide with previous reports showing an association between these polymorphisms and kidney disease, and along with other studies regarding their role in the nitric oxide pathway, suggest that these variants affect the severity of nephropathy in patients with FD.
Doctorado en Genética Humana, Instituto de Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.|División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
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Marin-Medina
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
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Brambila-Tapia
Laboratorio de Genética Humana, Unidad de Investigación, Facultad de Medicina, Universidad Autónoma de Sinaloa, Sinaloa, México.
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VJ
Picos-Cárdenas
División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
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Gallegos-Arreola
Doctorado en Genética Humana, Instituto de Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México luisfiguera@yahoo.com.|División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México luisfiguera@yahoo.com.
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D000328:Adult; D003404:Creatinine / Q000652:urine; D000795:Fabry Disease / Q000235:genetics* / Q000473:pathology / Q000652:urine; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000652:urine; D006801:Humans; D008297:Male; D008800:Mexico; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051437:Renal Insufficiency / Q000235:genetics* / Q000473:pathology / Q000652:urine; D012307:Risk Factors; D014508:Urea / Q000652:urine; D020663:ras Guanine Nucleotide Exchange Factors
D020662:Guanine Nucleotide Exchange Factors; C417242:RAPGEF5 protein, human; D020663:ras Guanine Nucleotide Exchange Factors; D014508:Urea; D003404:Creatinine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III