Genetic determinants of renal function across atrial fibrillation phenotypes in hypertensive patients: analysis of six polymorphisms
Z T Mashkurova, G J Abdullayeva, A A Abdullayev, X G Fozilov, B I Rozibaev, Sh H Namozova, M B SaidovaAbstract
Background
Renal dysfunction is frequent in arterial hypertension (HTN) and atrial fibrillation (AF). AF phenotypes may reflect different stages of cardiovascular remodelling, yet it remains unclear whether AF form independently contributes to renal impairment and whether genetic variants modify renal function.
Purpose
To assess estimated glomerular filtration rate (eGFR) across AF phenotypes and to evaluate associations of six genetic polymorphisms with renal function after adjustment for age and hypertension duration.
Methods
Baseline data from 223 patients with HTN and AF were analysed: paroxysmal (n=110), persistent (n=40), and permanent AF (n=73). The primary endpoint was eGFR (ml/min/1.73 m²) as a continuous variable. Microalbuminuria, urinary albumin-to-creatinine ratio (UACR), urinary creatinine, serum creatinine and uric acid were analysed as complementary renal markers. Six polymorphisms were tested: rs6817105, rs11773845, rs3807990, rs11264280, rs13376333, rs588837. Multivariable linear regression included AF form, age and hypertension duration. Genotype-by-AF form interaction was tested. Multiple comparisons were controlled using false discovery rate (FDR).
Results
Mean eGFR declined across AF phenotypes: 80.6±17.8 (paroxysmal), 72.1±17.3 (persistent) and 71.0±21.1 ml/min/1.73 m² (permanent). After adjustment for age and hypertension duration, AF form was not independently associated with eGFR (p=0.153), microalbuminuria (p=0.257), UACR (p=0.074), urinary creatinine (p=0.285) or uric acid (p=0.874), whereas serum creatinine remained associated with AF phenotype (p=0.0053). Age and hypertension duration were strong independent predictors of eGFR (both p<0.001). Among six polymorphisms, only rs11264280 showed an independent association with eGFR (p=0.000419): TT genotype was associated with ~6.45 ml/min/1.73 m² lower eGFR compared with the reference genotype, remaining significant after FDR correction (q≈0.018). No genotype-by-AF form interaction was detected for rs11264280 (p=0.290). rs6817105, rs11773845, rs3807990, rs13376333 and rs588837 showed no significant associations with renal parameters after adjustment and multiple testing correction (all p>0.05).
Conclusion
In hypertensive patients with AF, baseline eGFR differences across AF phenotypes are largely explained by age and hypertension duration rather than AF form itself. Among six tested variants, rs11264280 TT genotype is independently associated with lower eGFR, suggesting a potential genetic contribution to individual susceptibility to renal impairment irrespective of AF phenotype.