Gallbladder Disease 2

For a phenotypic description and a discussion of genetic heterogeneity of gallbladder disease (GBD), see GBD1 (600803).

Mapping

Using ultrasound-based information on GBD occurrence and a 10-cM gene map, Puppala et al. (2006) performed multipoint variance components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in San Antonio, Texas, were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. Five metabolic risk factors were defined: increased waist circumference, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The metabolic syndrome (605552) risk factor score (range 0 to 5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and metabolic syndrome risk factor score, Puppala et al. (2006) found stronger linkage signals for the symptomatic GBD phenotype. The highest lod scores (3.7 and 3.5) occurred on chromosome 1p between markers D1S1597 and D1S407 (1p36.21; GBD2) and near marker D1S255 (1p34.3; GBD3, 609919), respectively. Seven other genetic locations across the genome exhibited some evidence of linkage (lod equal to or greater than 1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of Lith loci, which influence gallstone formation in mouse models. In conclusion, Puppala et al. (2006) found significant evidence of major genetic determinants of symptomatic GBD on 1p in Mexican Americans.