'Linkage analysis of thyroid antibody production: evidence for shared susceptibility to clinical autoimmune thyroid disease.
BACKGROUND
Epidemiological data suggest a genetic susceptibility to thyroid antibody (TAb) production.


OBJECTIVE
The objective of the study was to identify genetic loci that are linked with TAb production.


METHODS
The design of the study was a whole genome linkage study in families with clustering of thyroid autoimmunity.


METHODS
The study took place at an academic medical center.


METHODS
Participants included 102 multigenerational families (540 individuals) multiplex for autoimmune thyroid disease (AITD) and TAb production.


METHODS
We computed two-point logarithm of odds (LOD) scores and multipoint heterogeneity LOD scores for 400 microsatellite markers spanning the entire human genome at an average distance of 10 cm (approximately 10 Mb).


RESULTS
Three loci showed evidence for linkage with TAb production: 1) 2q locus, which gave a maximum multipoint heterogeneity LOD score (HLOD) of 2.8 and contained the CTLA-4 gene, previously reported to be linked and associated with clinical AITD; (2) 6p locus (HLOD 2.5), which was the same AITD-1 locus found to be linked with clinical AITD; and (3) 8q locus (HLOD 2.2), which contained the thyroglobulin gene, also previously reported to be linked and associated with AITD. All loci that were linked to TAb were also linked to AITD, suggesting that TAb and AITD share the same genetic predisposition.


CONCLUSIONS
We conclude that: 1) some of the genes/loci predisposing to TAb and AITD are shared, whereas distinct genes/loci also exist; (2) the presence of TAb in relatives of AITD patients may be associated with increased risk for the development of clinical AITD; and (3) further studies are needed to determine the predictive value of TAb levels for the development of clinical AITD in relatives of patients with familial AITD.
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Yoshiyuki
Y
Ban
David A
DA
Greenberg
Terry F
TF
Davies
Eric
E
Jacobson
Erlinda
E
Concepcion
Yaron
Y
Tomer
D001323:Autoantibodies / Q000096:biosynthesis* / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics / Q000276:immunology; D050031:Hashimoto Disease / Q000235:genetics / Q000276:immunology; D006801:Humans; D008126:Lod Score; D008297:Male; D013959:Thyroid Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies