Association of hypertension and genetic variants in MYH9 and BMPR1B with increased proteinuria in sickle cell disease
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Sickle cell nephropathy (SCN) is a major chronic complication of sickle cell disease, and its progression may be influenced by genetic factors. This study aimed to investigate the association between variants in the MYH9 and BMPR1B genes and increased total proteinuria in patients with sickle cell anemia. MATERIALS AND METHODS: This cross-sectional study included patients with homozygous (SS) sickle cell disease who were followed up in Dakar. Urinary albumin, total proteins, and creatinine levels, along with serum creatinine and urea concentrations, were measured. Genotyping of the single nucleotide variants MYH9-rs4821469, MYH9-rs3752462, MYH9-rs2032487, and BMPR1B-rs17022863 was performed using mass spectrometry (MassARRAY technology). Associations were evaluated using multivariate logistic regression analysis. RESULTS: The 150-patient cohort had a mean age of 20.44 ± 9.86 years, with a slight female majority (51 %). A high prevalence of increased total proteinuria (urine proteins-to-creatinine ratio ≥150 mg/g) was observed, affecting 50.67 % of this young population. Multivariate analysis identified relative systemic hypertension (blood pressure ≥130/80 mmHg) as a powerful and independent risk factor for increased total proteinuria. While an initial analysis suggested a protective association for the MYH9 - rs4821469 variant, this signal was unstable and lost statistical significance in more stringent models. CONCLUSION: Increased total proteinuria is highly prevalent in this young cohort, indicating early onset of kidney damage. Relative systemic hypertension is a major modifiable risk factor, underscoring the need for rigorous blood pressure control. The instability of the initial genetic signal for MYH9-rs4821469, coupled with its strong linkage disequilibrium with APOL1, suggests that the observed association is likely confounded by ungenotyped APOL1 variants. This highlights the critical importance of including APOL1 analysis in future SCN genetic studies in African-ancestry populations.
Source: Clinical Biochemistry
Authors: El Hadji Malick Ndour, Khuthala Mnika, El Hadj Ousmane Sene, Fatou Gueye Tall, Victoria Nembaware, Indou Deme Ly, Moussa Seck, Mara Sokhna, Rokhaya Dione, Coumba Kamby, Jean Pascal Demba Diop, Serigne Saliou Mbacke, Nene Oumou Kesso Barry, Moustapha Djité, Pape Matar Kandji, Rokhaya Ndiaye Diallo, Ibrahima Diagne, Saliou Diop, Papa Madieye Gueye, Philomene Lopez Sall, Aynina Cisse, Ambroise Wonkam
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
OpenAlex ID: W4416416453