Trial reportNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2012
Methylenetetrahydrofolate reductase (MTHFR) polymorphism A1298C (Glu429Ala) predicts decline in renal function over time in the African-American Study of Kidney Disease and Hypertension (AASK) Trial and Veterans Affairs Hypertension Cohort (VAHC).
Trial report in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Regression methods for investigating risk factors of chronic kidney disease outcomes: the state of the art.BMC nephrology · 2014Pooled it
- Correlations of MTHFR 677C>T polymorphism with cardiovascular disease in patients with end-stage renal disease: a meta-analysis.PloS one · 2014Pooled it
- Genetic Variants in the MTHFR and WNK1 Genes and Their Contribution to Hypertension Susceptibility.International journal of medical sciences · 2026Article
- Investigation of the effects of MTHFR gene variations and homocysteine levels in hypertensive patients.Northern clinics of Istanbul · 2025Article
- Vitamin B12 deficiency in dialysis patients: risk factors, diagnosis, complications, and treatment: A comprehensive review.World journal of nephrology · 2024Review
- Towards Precision Medicine for Hypertension: A Review of Genomic, Epigenomic, and Microbiomic Effects on Blood Pressure in Experimental Rat Models and Humans.Physiological reviews · 2017Review
- Relationship of MTHFR gene polymorphisms with renal and cardiac disease.World journal of nephrology · 2015Article
- Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis.Journal of human hypertension · 2015Article
- Identifying multiple causative genes at a single GWAS locus.Genome research · 2013Article
- The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans.Cancer causes & control : CCC · 2013Article
- Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans.Kidney international · 2013Article
- No association of the MTHFR gene A1298C polymorphism with the risk of prostate cancer: A meta-analysis.Experimental and therapeutic medicine · 2012Article
- Target organ damage in African American hypertension: role of APOL1.Current hypertension reports · 2012Review
- Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.Current pharmacogenomics and personalized medicine · 2011Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundHyperhomocysteinemia is associated with increased venous thrombosis and cardiovascular disease (CVD). Mutations in the human methylenetetrahydrofolate reductase (MTHFR) gene have been associated with increased homocysteine levels and risks of CVD in various populations including those with kidney disease. Here, we evaluated the influence of MTHFR variants on progressive loss of kidney function.
methodsWe analyzed 821 subjects with hypertensive nephrosclerosis from the longitudinal National Institute of Diabetes and Digestive and Kidney Diseases African-American Study of Kidney Disease and Hypertension (AASK) Trial to determine whether decline in glomerular filtration rate (GFR) over ∼4.2 years was predicted by common genetic variation within MTHFR at non-synonymous positions C677T (Ala222Val) and A1298C (Glu429Ala) or by MTHFR haplotypes. The effect on GFR decline was then supported by a study of 1333 subjects from the San Diego Veterans Affairs Hypertension Cohort (VAHC), followed over ∼4.5 years. Linear effect models were utilized to determine both genotype [single-nucleotide polymorphism (SNP)] and genotype (SNP)-by-time interactions.
resultsIn AASK, the polymorphism at A1298C predicted the rate of GFR decline: A1298/A1298 major allele homozygosity resulted in a less pronounced decline of GFR, with a significant SNP-by-time interaction. An independent follow-up study in the San Diego VAHC subjects supports that A1298/A1298 homozygotes have the greatest estimated GFR throughout the study. Haplotype analysis with C677T yielded concurring results.
conclusionWe conclude that the MTHFR-coding polymorphism at A1298C is associated with renal decline in African-Americans with hypertensive nephrosclerosis and is supported by a veteran cohort with a primary care diagnosis of hypertension. Further investigation is needed to confirm such findings and to determine what molecular mechanism may contribute to this association.
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