Association of the MYH9 Gene Polymorphisms with Chronic Renal Disease Secondary to Hypertensive Nephrosclerosis, in a Caucasian Population
American Journal of Internal Medicine
Volume 2, Issue 6, November 2014, Pages: 95-101
Received: Sep. 8, 2014;
Accepted: Sep. 25, 2014;
Published: Oct. 30, 2014
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Diez-Ojea Beatriz, Nephrology Service, Hospital Universitario De Torrevieja-Vinalopo, Alicante, Spain
Marin Rafael, Nephrology Service, Centro Médico De Asturias, Oviedo (Asturias), Spain
Coto Eliecer, Laboratory of Molecular Genetics, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Tavira Beatriz, Laboratory of Molecular Genetics, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Fernandez-Vega Francisco, Nephrology Service, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Alvarez Rafael, Nephrology Service, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Fernandez-Fresnedo Gema, Nephrology Service, Hospital Universitario Marqués De Valdecilla, Santander (Cantabria), Spain
Pobes Alfonso, Nephrology Service, Hospital Valle Del Nalón, Langreo (Asturias), Spain
Suarez-Laures Ana, Nephrology Service, Hospital De Cabueñes, Gijón (Asturias), Spain
Garcia-Monteavaro Camino, Nephrology Service, Hospital San Agustín, Avilés (Asturias), Spain
Gorostidi Manuel, Nephrology Service, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Sanchez Emilio, Nephrology Service, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Arias Manuel, Nephrology Service, Hospital Universitario Marqués De Valdecilla, Santander (Cantabria), Spain
Ortega Francisco, Nephrology Service, Hospital Universitario Central De Asturias, Oviedo (Asturias), Spain
Background: Hypertensive nephrosclerosis (HN) is a chronic kidney disease (CKD) associated to essential hypertension, but their causal relationship is controversial. New evidence suggests that MYH9 gene alterations are associated with HN in African Americans. The aim of this study is to investigate the role of this gene in Spanish Caucasians. Methods: We compare high-risk MYH9 variants of patients with HN recruited according to standard clinical criteria (CKD stages 3-5), with essential hypertensives without renal disease (estimated glomerular filtration rate (eGFR) > 60 ml/min/1,73m2 and albuminuria < 300 mg/g creatinine), and also CKD patients with HN and progressive impairment of renal function with those who were stable. Diabetics were excluded. Results: A blood sample was obtained for genetic study of 238 patients with HN-CKD and 233 hypertensive controls. The rs3752462-T and rs4821480-T (risk alleles for CKD) were more frequent in the CKD group, but without significant difference. We found no differences for these SPNs with blood pressure, creatinine, albuminuria or renal disease progression. Conclusions: The effect of two common MYH9 single nucleotide polymorphisms (SPNs) on the development of CKD secondary to HN in our Spanish Caucasian population is low or zero; in any case less than that found in other, mainly African Americans.
Association of the MYH9 Gene Polymorphisms with Chronic Renal Disease Secondary to Hypertensive Nephrosclerosis, in a Caucasian Population, American Journal of Internal Medicine.
Vol. 2, No. 6,
2014, pp. 95-101.
Luke R. Hypertensive nephrosclerosis: pathogenesis and prevalence. Essential hypertension is an important cause of end-stage renal disease. Nephrol Dial Transplant 1999;14:2271-8.
Stengel B, Billon S, Van Dijk PC, et al. Trends in the incidence of renal replacement therapy for end-stage renal disease in Europe, 1990-1999. Nephrol Dial Transplant 2003;18:1824-33.
Siewert-Delle A, Ljungman S, Andersson OK, Wilhelmsen L. Does treated primary hypertension lead to end-stage renal disease? A 20-year follow-up of the Primary Prevention Study in Göteborg, Sweden. Nephrol Dial Transplant 1998;13:3084-90.
Skorecki KL, Wasser WG. Hypertension-misattributed kidney disease in African Americans. Kidney Int 2013;83:6-9.
Marcantoni C, Ma LJ, Federspiel C, Fogo AB. Hypertensive nephrosclerosis in African Americans versus Caucasians. Kidney Int 2002;62:172-80.
Kao WH, Klag MJ, Meoni LA, et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 2008;40:1185-92.
Kopp JB, Smith MW, Nelson GW, et al. MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 2008;40:1175-84.
Freedman BI, Hicks PJ, Bostrom MA, et al. Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans. Kidney Int 2009;75:736-45.
Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010;329:841-5.
Lipkowitz MS, Freedman BI, Langefeld CD, et al. Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int 2013;83:114-20.
Parsa A, Kao WHL, Xie D, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med 2013 Nov 9. [Epub ahead of print].
Pattaro C, Aulchenko YS, Isaacs A, et al. Genome- wide linkage analysis of serum creatinine in three isolated European populations. Kidney Int 2009;76:297-306.
O'Seaghdha CM, Parekh RS, Hwang SJ, et al. The MYH9/APOL1 region and chronic kidney disease in European-Americans. Hum Mol Genet 2011;20:2450-6. .
Cooke JN, Bostrom MA, Hicks PJ, et al. Polymorphisms in MYH9 are associated with diabetic nephropathy in European Americans. Nephrol Dial Transplant 2012;27:1505-11.
McKnight AJ, Duffy S, Fogarty DG, Maxwell AP. Association of MYH9/APOL1 with chronic kidney disease in a UK population. Nephrol Dial Transplant 2012(27):3660.
Tavira B, Coto E, Gómez J, et al. Association between a MYH9 polymorphism (rs3752462) and renal function in the Spanish RENASTUR cohort. Gene 2013;520(1):73-6.
Diez Ojea B, Marin R, Coto E, et al. Clinical and genetic bases of Hipertensive Nephrosclerosis. NEFROSEN Study. Nefrología 2010;30(6):687-97.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130, 461-70.
Freedman BI, Langefeld CD. The new era of APOL1-associated glomerulosclerosis. Nephrol Dial Transplant 2012;27:1288-91.
Wang G, Lai FM, Kwan BC, et al. Podocyte Loss in Human Hypertensive Nephrosclerosis. Am J Hypertens 2009;22:300-6.
Freedman BI, Langefeld CD, Turner J, et al. Association of APOL1 variants with mild kidney disease in the first-degree relatives of African American patients with non-diabetic end-stage renal disease. Kidney Int 2012;82:805-11.
Murea M, Freedman BI. Essential hypertension and risk of nephropathy: a reappraisal. Curr Opin Nephrol Hypertens 2010;19:235-41.
Singh N, Nainani N, Arora P, Venuto RC. CKD in MYH9-Related Disorders. Am J Kidney Dis 2009;54:732-40.
Vikse BE, Aasarød K, Bostad L, Iversen BM. Clinical prognostic factors in biopsy- proven benign nephrosclerosis. Nephrol Dial Transplant 2003;18:517-23.
Jafar TH, Stark PC, Schmid CH, et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int 2001;60:1131-40.
Freedman BI, Murea M. Target organ damage in African American hypertension: role of APOL1. Curr Hypertens Rep 2012;14:21-8.