Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome

Giuseppe Barbesino, Yaron Tomer, Erlinda S. Concepcion, Terry F. Davies, David A. Greenberg, Rhoda Cobin, Luca Chiovato, Aldo Pinchera, Sandra McLachlan, Bernard Rees Smith, Fred Clark, Eric Young, Meir Berezin

Research output: Contribution to journalArticle

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Abstract

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor a and β and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor α and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor β could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor α and the aromarase genes in the genetic predisposition to AITD. Estrogen receptor β remains a candidate locus. We found a locus on Xq21.33- 22 linked to GD that may help to explain the female predisposition to GD. Confirmation of these data in HT may require study of an extended number of families because of possible heterogeneity.

Original languageEnglish (US)
Pages (from-to)3290-3295
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number9
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

X-Linked Genes
Graves Disease
Thyroid Diseases
Genetic Association Studies
Chromosomes
Autoimmune Diseases
Genes
Hashimoto Disease
Estrogen Receptors
X Chromosome
Aromatase
Chromosomes, Human, Pair 22
Chromosome Mapping
Genetic Predisposition to Disease
Microsatellite Repeats
Estrogens
Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. / Barbesino, Giuseppe; Tomer, Yaron; Concepcion, Erlinda S.; Davies, Terry F.; Greenberg, David A.; Cobin, Rhoda; Chiovato, Luca; Pinchera, Aldo; McLachlan, Sandra; Smith, Bernard Rees; Clark, Fred; Young, Eric; Berezin, Meir.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 9, 1998, p. 3290-3295.

Research output: Contribution to journalArticle

Barbesino, G, Tomer, Y, Concepcion, ES, Davies, TF, Greenberg, DA, Cobin, R, Chiovato, L, Pinchera, A, McLachlan, S, Smith, BR, Clark, F, Young, E & Berezin, M 1998, 'Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome', Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 9, pp. 3290-3295. https://doi.org/10.1210/jc.83.9.3290
Barbesino, Giuseppe ; Tomer, Yaron ; Concepcion, Erlinda S. ; Davies, Terry F. ; Greenberg, David A. ; Cobin, Rhoda ; Chiovato, Luca ; Pinchera, Aldo ; McLachlan, Sandra ; Smith, Bernard Rees ; Clark, Fred ; Young, Eric ; Berezin, Meir. / Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 9. pp. 3290-3295.
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AU - Davies, Terry F.

AU - Greenberg, David A.

AU - Cobin, Rhoda

AU - Chiovato, Luca

AU - Pinchera, Aldo

AU - McLachlan, Sandra

AU - Smith, Bernard Rees

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