Single nucleotide polymorphism SULT2A1 rs4149448 and genetic risk score as biomarkers of frailty and progression of chronic kidney disease.

BACKGROUND

Frailty is a multifactorial condition highly prevalent in patients with chronic kidney disease (CKD), increasing with disease progression. Identifying genetic determinants associated with frailty may aid in risk stratification. We aimed to identify whether single nucleotide polymorphisms (SNPs), individually or combined into a genetic risk score (GRS), are associated with the frailty phenotype and adverse clinical outcomes in CKD patients.

METHODS

This is a longitudinal study that evaluated patients with CKD 3b-5 non-dialysis dependent [69 (57-72) years; 59,1 % men; body mass index, 27.2 ± 5.3 kg/m2]. Clinical, anthropometric, and biochemical variables, including 25(OH)D concentration, were evaluated. Eight SNPs associated with low vitamin D levels were genotyped using qPCR. The genetic risk score (GRS) was calculated by summing the number of risk alleles for vitamin D deficiency across the SNPs, resulting in values ranging from 0 to 16. Frailty was assessed using the physical frailty phenotype. The outcomes considered were non-elective hospitalization and changes in CKD stage.

RESULTS

Around 36 % of patients were frail, and 68 % had 25(OH)D levels below 20 ng/mL and were considered deficient. The higher GRS [9 (7-10) versus 6 (5-7); p = 0.034] occurred in patients who developed CKD progression. After the adjusted logistic regression analysis, the SULT2A1 genotype of rs4149448 was associated with a greater chance of frailty (OR: 8.8 IC95% 1.048-74.733; p = 0.045).

CONCLUSION

Specific genetic variants, including a higher GRS and the SNP SULT2A1 rs4149448 genotype, were associated with CKD progression and frailty, suggesting their potential role in risk stratification.