PURPOSE: Microalbuminuria, defined as urine albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg, is a major risk factor for cardiovascular disease. Several genetic epidemiological studies have established that microalbuminuria clusters in families, suggesting a genetic predisposition. METHOD: We estimated heritability of microalbuminuria and performed a genome-wide linkage analysis to identify chromosomal regions influencing urine albumin-to-creatinine ratio in 486 Mexican Americans from 26 multiplex families. RESULTS: Significant heritability was demonstrated for urine albumin-to-creatinine ratio (h = 24%, P < 0.003) after accounting for age, sex, body mass index, triglycerides, and hypertension. Genome scan revealed significant evidence of linkage of urine albumin-to-creatinine ratio to a region on chromosome 20q12 (LOD score of 3.5, P < 0.001) near marker D20S481. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with hypertension status as a covariate suggesting that the effect of this locus on urine albumin-to-creatinine ratio is largely independent of diabetes and hypertension. CONCLUSION: Findings indicate that there is a gene or genes located on human chromosome 20q12 that may have functional relevance to albumin excretion in Mexican Americans. Identifying and understanding the role of the genes that determine albumin excretion would lead to the development of novel therapeutic strategies targeted at high-risk individuals in whom intensive preventive measures may be most beneficial.
PURPOSE: Microalbuminuria, defined as urine albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg, is a major risk factor for cardiovascular disease. Several genetic epidemiological studies have established that microalbuminuria clusters in families, suggesting a genetic predisposition. METHOD: We estimated heritability of microalbuminuria and performed a genome-wide linkage analysis to identify chromosomal regions influencing urine albumin-to-creatinine ratio in 486 Mexican Americans from 26 multiplex families. RESULTS: Significant heritability was demonstrated for urine albumin-to-creatinine ratio (h = 24%, P < 0.003) after accounting for age, sex, body mass index, triglycerides, and hypertension. Genome scan revealed significant evidence of linkage of urine albumin-to-creatinine ratio to a region on chromosome 20q12 (LOD score of 3.5, P < 0.001) near marker D20S481. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with hypertension status as a covariate suggesting that the effect of this locus on urine albumin-to-creatinine ratio is largely independent of diabetes and hypertension. CONCLUSION: Findings indicate that there is a gene or genes located on human chromosome 20q12 that may have functional relevance to albumin excretion in Mexican Americans. Identifying and understanding the role of the genes that determine albumin excretion would lead to the development of novel therapeutic strategies targeted at high-risk individuals in whom intensive preventive measures may be most beneficial.
Authors: Nedal H Arar; Venkata S Voruganti; Subrata D Nath; Farook Thameem; Richard Bauer; Shelley A Cole; John Blangero; Jean W MacCluer; Anthony G Comuzzie; Hanna E Abboud Journal: Nephrol Dial Transplant Date: 2008-04-28 Impact factor: 5.992
Authors: Madhumathi Rao; Amy K Mottl; Shelley A Cole; Jason G Umans; Barry I Freedman; Donald W Bowden; Carl D Langefeld; Caroline S Fox; Qiong Yang; Adrienne Cupples; Sudha K Iyengar; Steven C Hunt; Thomas A Trikalinos Journal: Nephrol Dial Transplant Date: 2011-05-28 Impact factor: 5.992
Authors: Carmen A Peralta; Yongmei Li; Christina Wassel; Shweta Choudhry; Walter Palmas; Michael F Seldin; Neil Risch; David Siscovick; Donna Arnett; Bruce Psaty; Michael G Shlipak Journal: Circ Cardiovasc Genet Date: 2010-05-05
Authors: Amy K Mottl; Suma Vupputuri; Shelley A Cole; Laura Almasy; Harald H H Göring; Vincent P Diego; Sandra Laston; Nawar Shara; Elisa T Lee; Lyle G Best; Richard R Fabsitz; Jean W MacCluer; Jason G Umans; Kari E North Journal: J Am Soc Nephrol Date: 2009-04-15 Impact factor: 10.121