Source: American Physiological Society (APS)

Released: Fri 19-Oct-2001, 00:00 ET  Embargo expired: Thu 18-Oct-2001, 00:00 ET  Printer-friendly Version

Transmitting Susceptibility to Autoimmune Diseases

EMBARGOED UNTIL OCTOBER 18, 2001
Contact: Donna Krupa
703.527.7357 (OFFICE)
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OR IN THE APS Newsroom @ The Westin Convention Center
Pittsburgh, PA October 17-20, 2001
Tel: 412.281.3700 (The Crawford Room)

FATHERS PLAY THE KEY ROLE IN TRANSMITTING SUSCEPTIBILITY TO AUTOIMMUNE DISEASES TO THEIR DAUGHTERS

Researchers find that hormones and X-chromosomal genes may play a role in gender-specific susceptibility to endocrine disorders.

PITTSBURGH, Pa. - Thyroid autoimmune disorders such as Graves' disease (GD) or Hashimoto's thyroiditis (HT) and other autoimmune diseases have a strong, yet unexplained female preponderance. At the same time, some human lymphocyte antigens (HLA) susceptibility alleles found in Type 1 diabetes mellitus (TlDM) point to a higher risk for boys than girls.

Type 1 diabetes is one of the most frequent chronic diseases in children. Although it is an autoimmune disorder, its etiology remains unclear. However, there is considerable evidence that both genetic and environmental factors are major determinants. As a genetic marker, Type 1 diabetes is primarily determined by genes in the HLA region of chromosome 6.

The authors of the study, "Evidence For Gender-Specific Effects On the Transmission of Androgen Receptor Does Not Play A Role In The Thymic HLA Susceptibilily Alleles To Patients With Graves' Disease, Hashimoto's Thyroiditis As Well As Type 1 Diabetes Mellitus," are K. Badenhoop, T. Siegmund and M.A. Pani, of the Department of Endocrinology, University Hospital, Frankfurt/Main, Germany; M. Segni of the Department of Pediatrics, University La Sapienza, Rome, Italy; and J. Ramser and A. Meindl, both from the Department of Medical Genetics, Children's Hospital, University of Munich, Germany. Their findings are being presented in detail at the upcoming conference, Genomes and Hormones: An Integrative Approach to Gender Differences in Physiology, being sponsored by the American Physiological Society (APS). The conference is being held October 17-20, 2001 at the Westin Convention Center, Pittsburgh, PA.

Methodology and Results
The researchers investigated patients with Graves' disease, Hashimoto's thyroiditis or Type 1 Diabetes Mellitus -- and their parents -- to identify transmission of high risk HLA DQ alleles using standard sequence-specific typing methods. Altogether 1347 individuals were investigated of which 130 individuals and their parents had thyroid autoimmune disorders ( 12 with GD, 91 with HT and 346 with T1DM).

-- There was significant susceptibility for both GD and HT associated with DQ2 alleles that was most pronounced when transmitted from fathers to affected daughters.

-- In TlDM patients, the DQ8 haplotype was found significantly more often to be transmitted by fathers than by mothers to affected offspring (p=0.005) mainly due to a preferential transmission of DQ8 by fathers to affected daughters.

Conclusions
These results suggest an X-chromosomal factor interact with HLA DQ haplotypes in Graves' disease, Hashimoto's thyroiditis or Type 1 Diabetes Mellitus. In addition, hormonal factors may regulate this interaction since some of the observed transmission differences disappear when pre- and postpubertal manifestation of disease is separately analyzed. Thus, both X-chromosomal genes and hormones may play a role in sex-specific susceptibility to endocrine autoimmunity.

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The American Physiological Society (APS) was founded in 1887
to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000
members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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Editor's Note: To set up an interview with Dr. Badenhoop, please contact Donna Krupa in the APS newsroom at 412.281.3700 (The Crawford Room).After newsroom hours, contact 703.967.275l (cell), 703.527.7357 (office) or djkrupa1@aol.com (email).