The Effect of Smoking on Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease Patients with Preserved Renal Function

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of PKD1/2 were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the PKD1 gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel. PKD1 protein-truncating (PKD1-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to PKD1 non-truncating and PKD2 genotypes. The PKD1 genotype showed earlier onset of ESRD compared to PKD2 genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect, PKD2 genotype had 0.2 times lower risk for reaching ESRD than PKD1-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans.

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Angiotensin-converting enzyme gene polymorphism in autosomal dominant polycystic kidney disease

National Journal of Clinical Anatomy ◽

10.1055/s-0039-3401746 ◽

2014 ◽

Vol 03 (02) ◽

pp. 057-063 ◽

Cited By ~ 1

Author(s):

Sanjeev Nair ◽

Praveen Kumar Kolla ◽

Madhav Desai ◽

Pathapati Rama Mohan ◽

Ramalingam K. ◽

...

Keyword(s):

Renal Function ◽

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Genotype Distribution ◽

Polycystic Kidney ◽

Ace Genotype ◽

Autosomal Dominant Polycystic Kidney ◽

Rate Of Decline ◽

The One

Abstract Background and aim : Autosomal dominant polycystic kidney disease shows considerable variability in clinical features, including differences in severity of hypertension, rate of decline of renal function and variability in rate of cystogenesis, which are not fully explained by the genetic heterogeneity of this disease. Many different modifier variables have been proposed to explain this variability. This study aims to look at the role played by polymorphism of the ACE gene as a possible modifier in the clinical course and rapidity of progression. Material and Methods : Thirty seven patients diagnosed as ADPKD were recruited to the study. Clinical data were provided by questionnaires. Blood was collected for the determination of the ACE Insertion/Deletion (I/D) polymorphism genotype. The ACE genotype was also determined in a general control population (n = 40). The data was analyzed using the SPSS software. ACE genotype polymorphism frequencies were compared across groups using the one-way ANOVA tests. λ2 cross tabulation statistics was used to test for difference between frequency data. Results: The ACE genotype distribution showed no differences between the study (II 29.7%, ID 43.2%, DD 27.1%) and the control (II 35%, ID 45%, DD 20%) populations. Although patients on hemodialysis had a significantly higher Blood Pressure levels (p = 0.004) when compared to non-dialysis patients, no significant differences were demonstrated between genotypes of the study population. No difference was also demonstrated between the genotypes for rate of decline in renal function. Conclusion : No relationship between the ACE I/D polymorphism in ADPKD patients and severity of hypertension or progression towards ESRD was demonstrated.

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