Abstract P309: The Association of the CUBN Polymorphism rs1801239 and the Association of Albuminuria and Cardiovascular Disease in the Framingham Heart Study
Background: Albuminuria is a risk factor for cardiovascular disease (CVD). A missense SNP (rs1801239) in the CUBN gene, which encodes for a proximal tubular protein responsible for retrieving filtered proteins from the urine, has been associated with albuminuria in a genome-wide association study. It is unclear if, in the absence of other risk factors, albuminuria associated with this SNP may be benign and thus not carry the same cardiovascular risk as albuminuria in the absence of the SNP. We hypothesized that albuminuria associated with this SNP would be associated with CVD irrespective of the presence of the mutation.
Methods: We analyzed participants from the Framingham Heart Study Offspring and Third Generation cohorts (n=6399, mean age 47 years, 53.4% women). The urinary albumin to creatinine ratio (UACR) was measured on spot morning urines and microalbuminuria (MA) was defined as a UACR≥17mg/g [men] and ≥25mg/g [women]. Direct genotyping of rs1801239 was performed and participants were dichotomized according to whether or not they carried at least one copy of the minor allele. Participants were followed for 10.4 years. Cox proportional hazards models were used to evaluate the association between albuminuria and incident CVD stratified by the presence or absence of the minor allele after accounting for traditional CVD risk factors. Finally, using an interaction term for albuminuria with rs1801239, we evaluated whether the addition of the minor allele to the model altered the association between albuminuria and CVD.
Results: Overall, 21% of participants carried at least one copy of the minor allele. As expected, those carrying at least one copy of the minor allele had a higher prevalence of albuminuria (10.7% vs. 8.9%) compared to the rest of the sample. During follow-up, 5.6% (n=346) of participants had a CVD event. MA at baseline was associated with an increased risk of CVD (HR 1.46, 95%CI 1.36-2.24), but there was no interaction between MA and rs1801239 on CVD (pinteraction=0.47). When stratified by carriers of the minor allele, the HR for CVD was 2.32 (95%CI 1.41-3.82) among those with at least one copy of the minor allele as compared to 1.59 (95%CI 1.19-2.14) in the rest of the sample.
Conclusion: Albuminuria is associated with CVD irrespective of the CUBN risk allele at rs1801239. These results challenge the concept that albuminuria in the setting of the CUBN mutation is benign.
- © 2013 by American Heart Association, Inc.