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J Steroid Biochem Mol Biol. 2017 Nov;174:169-175. doi: 10.1016/j.jsbmb.2017.08.017. Epub 2017 Sep 1.

Relationship of SULT1A1 copy number variation with estrogen metabolism and human health.

Author information

1
Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
2
Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI, USA.
3
A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA.
4
A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA; Division of Infectious Diseases, Children's Hospital of Philadelphia, PA, USA.
5
Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI, USA. Electronic address: hebbring.scott@mcrf.mfldclin.edu.

Abstract

Human cytosolic sulfotransferase 1A1 (SULT1A1) is considered to be one of the most important SULT isoforms for metabolism, detoxification, and carcinogenesis. This theory is driven by observations that SULT1A1 is widely expressed in multiple tissues and acts on a wide range of phenolic substrates. SULT1A1 is subject to functional common copy number variation (CNV) including deletions or duplications. However, it is less clear how SULT1A1 CNV impacts health and disease. To better understand the biological role of SULT1A1 in human health, we genotyped CNV in 14,275 Marshfield Clinic patients linked to an extensive electronic health record. Since SULT1A1 is linked to steroid metabolism, select serum steroid hormones were measured in 100 individuals with a wide spectrum of SULT1A1 CNV genotypes. Furthermore, comprehensive phenome-wide association studies (PheWAS) were conducted using diagnostic codes and clinical text data. For the first time, individuals homozygous null for SULT1A1 were identified in a human population. Thirty-six percent of the population carried >2 copies of SULT1A1 whereas 4% had ≤1 copy. Results indicate SULT1A1 CNV was negatively correlated with estrone-sulfate to estrone ratio predominantly in males (E1S/E1; p=0.03, r=-0.21) and may be associated with increased risk for common allergies. The effect of SULT1A1 CNV on circulating estrogen metabolites was opposite to the predicted CNV-metabolite trend based on enzymatic function. This finding, and the potential association with common allergies reported herein, warrants future studies.

KEYWORDS:

Allergy; Estrogen; Metabolism; PheWAS; SULT1A1; Sulfation; TextWAS

PMID:
28867356
PMCID:
PMC5675753
DOI:
10.1016/j.jsbmb.2017.08.017
[Indexed for MEDLINE]
Free PMC Article

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