Significant intrafamilial phenotypic variability is well documented in autosomal dominant polycystic kidney disease (ADPKD) and suggests a modifier effect. In this study, variance components analysis was performed to estimate the contribution of genetic factors for within-family renal disease variability in 406 patients from 66 type 1 ADPKD families. Overall, 39% of the study patients had ESRD at their last follow-up, and their renal survival did not differ by gender (P = 0.35, log-rank test). Because their frequency plot of creatinine clearance (Ccr) assumed a bimodal distribution with a marked kurtosis that was not improved by transformations, the study cohort was decomposed into two separate groups (non-ESRD [n = 247] and ESRD [n = 159]) in which the Ccr plots were normally distributed. The heritability (h(2)) of Ccr and age at ESRD (age(ESRD)) and the genetic correlations between these measures and their covariates were estimated. In patients without ESRD, a significant heritability was found for Ccr (h(2) = 0.42; P = 0.0015) after adjusting for age (P = 0.0001), systolic BP (P = 0.0006), and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P = 0.00001). Birth year, gender, BMI, diastolic and mean BP, and pack-years of cigarette smoking did not significantly influence the heritability of this trait. In patients with ESRD, age(ESRD) provides a better measure than Ccr, which was very narrowly distributed. A significant heritability was found for ageESRD (h(2) = 0.78; P = 0.00009) in these latter patients. None of the above covariates influenced the heritability of this trait. It is concluded that a significant modifier gene effect influences the progression of renal disease in type 1 ADPKD.

Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease / Ad, Paterson; Magistroni, Riccardo; N., He; Kr, Wang; A., Johnson; Pr, Fain; E., Dicks; P., Parfrey; P., St George Hyslop; Y., Pei. - In: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. - ISSN 1046-6673. - STAMPA. - 16:(2005), pp. 755-762.

Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease

MAGISTRONI, Riccardo;
2005-01-01

Abstract

Significant intrafamilial phenotypic variability is well documented in autosomal dominant polycystic kidney disease (ADPKD) and suggests a modifier effect. In this study, variance components analysis was performed to estimate the contribution of genetic factors for within-family renal disease variability in 406 patients from 66 type 1 ADPKD families. Overall, 39% of the study patients had ESRD at their last follow-up, and their renal survival did not differ by gender (P = 0.35, log-rank test). Because their frequency plot of creatinine clearance (Ccr) assumed a bimodal distribution with a marked kurtosis that was not improved by transformations, the study cohort was decomposed into two separate groups (non-ESRD [n = 247] and ESRD [n = 159]) in which the Ccr plots were normally distributed. The heritability (h(2)) of Ccr and age at ESRD (age(ESRD)) and the genetic correlations between these measures and their covariates were estimated. In patients without ESRD, a significant heritability was found for Ccr (h(2) = 0.42; P = 0.0015) after adjusting for age (P = 0.0001), systolic BP (P = 0.0006), and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P = 0.00001). Birth year, gender, BMI, diastolic and mean BP, and pack-years of cigarette smoking did not significantly influence the heritability of this trait. In patients with ESRD, age(ESRD) provides a better measure than Ccr, which was very narrowly distributed. A significant heritability was found for ageESRD (h(2) = 0.78; P = 0.00009) in these latter patients. None of the above covariates influenced the heritability of this trait. It is concluded that a significant modifier gene effect influences the progression of renal disease in type 1 ADPKD.
16
755
762
Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease / Ad, Paterson; Magistroni, Riccardo; N., He; Kr, Wang; A., Johnson; Pr, Fain; E., Dicks; P., Parfrey; P., St George Hyslop; Y., Pei. - In: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. - ISSN 1046-6673. - STAMPA. - 16:(2005), pp. 755-762.
Ad, Paterson; Magistroni, Riccardo; N., He; Kr, Wang; A., Johnson; Pr, Fain; E., Dicks; P., Parfrey; P., St George Hyslop; Y., Pei
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/307038
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