Studies of Nuclear Receptors in Disease

Single nucleotide polymorphisms (SNPs) are base pair changes which exist naturally in a population. Usually variants which occur at an allele frequency exceeding 1% are referred to as SNPs. SNPs provide important tools for human genetic studies.

A set of polymorphisms are scored in cases and controls. If an association is detected, i. e. a specific nucleotide is more common at one position in the gene in cases compared to controls, this indicates that the polymorphism per se, or some other change in the same or neighboring genes, is related to disease.

For several decades it has been known that estrogens are essential for human health. The discovery that there are two estrogen receptors (ER), ERα and ERβ, has facilitated our understanding of how the hormone exerts its physiological effects. A number of polymorphisms have been reported in the ERs. Association between SNPs in ER genes and disease have been demonstrated in several cases. We have shown that variants of ERβ are associated with bulimia. In separate studies, we have shown that mutations in ERβ are not the cause of a number of human syndromes, including breast cancer, prostate cancer and different forms of female infertility, at least not in the populations under study.

References

Nilsson Maria, Naessén Sabine, Dahlman Ingrid, Lindén Hirschberg Angelica, Gustafsson Jan-Åke, and Dahlman-Wright Karin.
Association of Estrogen Receptor β Gene Polymorphisms with Bulimic Disease in Women.
Molecular Psychiatry 9(1): 28-34. 2004.

Maria Nilsson, Karin Dahlman-Wright and Jan-Åke Gustafsson.
Nuclear Receptors and Disease – the Oestrogen Receptors.
Essays Biochem. 2004;40:157-67.

Heldring N, Nilsson M, Buehrer B, Treuter E and Gustafsson J-Å.
Identification of novel subtype-specific binding peptides reveals insights into tamoxifen action on estrogen receptors ERα and β.
Mol Cell Biol. 2004 Apr;24(8):3445-59.

Birgitta Glenmark, Maria Nilsson, Hui Gao, Jan-Åke Gustafsson, Karin Dahlman-Wright, Håkan Westerblad. Difference in Skeletal Muscle Function in Males vs Females; Role of Estrogen Receptor β.
Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1125-31.