Back to Search
Start Over
Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones-Role of Age and Comorbid Diseases.
- Source :
-
PLoS Genetics . Jul2010, Vol. 6 Issue 7, p1-9. 9p. 4 Charts, 2 Graphs. - Publication Year :
- 2010
-
Abstract
- Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P= 4.1×10-10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P= 1.3×10-23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P= 3.0×10-17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P =1.0×10-6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P= 5.7×10-5). [ABSTRACT FROM AUTHOR]
- Subjects :
- *KIDNEY diseases
*DISEASES
*MORTALITY
*KIDNEY stones
*DIABETES
*HYPERTENSION
Subjects
Details
- Language :
- English
- ISSN :
- 15537390
- Volume :
- 6
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- PLoS Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 52848958
- Full Text :
- https://doi.org/10.1371/journal.pgen.1001039