Résumé
Objective: This study aimed to investigate the association of single nucleotide polymorphism (SNP) of UMOD gene (three SNP at promoter region; rs13333226, rs12917707, and rs4293393) with albuminuria and other renal function biomarkers in patients with type-2 diabetes mellitus. Methods: A case-control study design was employed to enroll 120 subjects, where 30 healthy subjects (as control group), 30 diabetic patients with normo-albuminuria (as first case group), 30 diabetic patients with microalbuminuria (as second case group) and 30 diabetic patients with macroalbuminuria (as third case group) were involved. Blood and urine samples were collected from the patients during their visits to diabetic clinics. Age, gender and BMI were taken for each participant. Fasting serum glucose (FSG), serum creatinine and blood urea were measured by a spectrophotometer, serum cystatin-c by ELISA technique, HbA1c was measured by the CLOVER A1c system, urinary albumin was measured by turbidimetric end-point method, (UACR) urinary albumin creatinine ratio were estimated, eGFR was also calculated. A whole blood sample was used for DNA extraction, finally, real time PCR technique was used for the determination of SNP genotype. Results: The results showed that the G minor allele of rs13333226 has a protective factor in patients with albuminuria. Also, the common variant AA of rs13333226 genotype was associated with a reduction in GFR. For the rs12917707 the common variant GG was associated with the development of albuminuria in diabetic patients and with the reduction in GFR. Finally, the frequency of (rs4293393) CC genotype was common and associated with the development of albuminuria in diabetic patients when compared with healthy controls. Conclusions: SNP in the regulatory region of the UMOD gene has a role in the protection from albuminuria in diabetes mellitus patients.
Résumé
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is characterized by autosomal dominant inheritance, progressive chronic kidney disease, and a bland urinary sediment. ADTKD is most commonly caused by mutations in the UMOD gene encoding uromodulin (ADTKD-UMOD). We herein report the first confirmed case of a multi-generational Brazilian family with ADTKD-UMOD, caused by a novel heterozygous mutation (c.163G>A, GGC→AGC, p.Gly55Ser) in the UMOD gene. Of 41 family members, 22 underwent genetic analysis, with 11 individuals found to have this mutation. Three affected individuals underwent hemodialysis, one peritoneal dialysis, and one patient received a kidney transplant from a family member later found to be genetically affected. Several younger individuals affected with the mutation were also identified. Clinical characteristics included a bland urinary sediment in all tested individuals and a kidney biopsy in one individual showing tubulointerstitial fibrosis. Unlike most other reported families with ADTKD-UMOD, neither gout nor hyperuricemia was found in affected individuals. In summary, we report a novel UMOD mutation in a Brazilian family with 11 affected members, and we discuss the importance of performing genetic testing in families with inherited kidney disease of unknown cause.