Abstract 2382: Genome-Wide Linkage Scan to Identify Loci for Albuminuria in the San Antonio Family Heart Study
Microalbuminuria (MA) is a major risk factor for cardiovascular disease (CVD). Microalbuminuria is defined as urine albumin/creatinine ratio (ACR) mg/mg range (0.03– 0.3) . Several genetic epidemiological studies have established that microalbuminuria clusters in families suggesting that there is a genetic predisposition. We estimated heritability of albuminuria and performed a genome wide scan/linkage analysis to identify chromosomal regions influencing ACR in Mexican Americans enrolled in the San Antonio Family Heart Study (SAFHS). We used variance components linkage analysis, as implemented in the program SOLAR, to perform the linkage analysis on 484 participants from 26 multiplex families of the SAFHS. A total of 417 microsatellite markers were genotyped at an average interval of 10 cM spanning 22 autosomal chromosomes. ACR revealed significant heritability (h2 = 24%, p<0.003) after accounting for the covariate effects of age and sex, BMI, triglycerides (TG), and hypertension status systolic blood pressure (SBP). We performed a multipoint linkage analysis and found significant evidence for linkage of ACR to a region on chromosome 20q12 (LOD score of 3.5, p<0.001) near marker D20S48. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with SBP as a covariate suggesting that the effect of this locus on albuminuria is largely independent of diabetes and hypertension. Findings indicate that there is a gene or genes located on human chromosome 20q12 that may have functional relevance to albuminuria in Mexican Americans. Several genome-wide scans for type 2 diabetes susceptibility loci have also identified linkage on chromosome 20q12–13, in a region that encompasses HNF4A and PTP1B. Plans are under way to map, characterize and identify polymorphic gene(s) that influence susceptibility to albuminuria on 20q12. Identifying and understanding the role of albuminuria gene(s) in the development of complex diseases such as CVD would increase our knowledge about the mechanism and pathophysiology of CVD. Also, it may lead to the development of novel therapeutic strategies targeted at high risk individuals in whom intensive preventive measures may be most beneficial.