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Autoimmune thyroid disease susceptibility loci in a large Chinese family
R Villanueva1, Y Tomer, D A Greenberg
1Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. ronald.villanueva@mssm.edu
Objectives:
The autoimmune thyroid diseases (AITDs) comprising Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases, which result from an interaction between predisposing genes and environmental triggers. The aim of our study was to dissect the genetic predisposition to GD and HT in one large Chinese family with multiple members affected with AITD.
Patients:
We completed a whole genome screen of a large multiplex Chinese-American family. We enrolled 27 family members from three generations. Eight members were affected with AITD, six had GD and two had HT.
Design:
We determined the information limits of the family. Power calculations indicated that the maximum attainable LOD scores were 5.1 assuming dominant inheritance, and 3.4 assuming recessive inheritance. These estimates both assumed 100% penetrance and one gene. Whole genome screening was performed using 400 highly polymorphic and densely spaced microsatellite markers spanning the entire human genome (intermarker distance < 10 cM). Linkage analysis was performed using two-point and multipoint parametric and nonparametric methods.
Results:
Initial whole genome screening performed with 400 microsatellite markers identified two markers that showed evidence for linkage to AITD in this family, D11S4191 and D9S175, with two-point LOD scores of 2.31 and 2.05, respectively. Multipoint linkage analysis focusing on the regions containing these markers revealed a maximum multipoint LOD score (MLS) of 2.13 and a nonparametric linkage score (NPL) of 6.1 for D11S4191 and an MLS of 2.01 and NPL of 7.5 for D9S175.
Conclusions:
These results showed that this Chinese family harboured susceptibility loci for AITD which were distinct from those previously found in the Caucasian population. This suggests that different susceptibility loci exist between different ethnic groups. Furthermore, even within a single family from a genetically homogenous population, more than one gene was involved in the genetic susceptibility to AITD, supporting the notion that AITDs are caused by multiple genes of varying influences.