Glucocorticoid receptor gene variant in the 3' untranslated region is associated with multiple measures of blood pressure.

TitleGlucocorticoid receptor gene variant in the 3' untranslated region is associated with multiple measures of blood pressure.
Publication TypeJournal Article
Year of Publication2009
AuthorsChung, CC, Shimmin, L, Natarajan, S, Hanis, CL, Boerwinkle, E, Hixson, JE
JournalJ Clin Endocrinol Metab
Date Published2009 Jan
Keywords3' Untranslated Regions, Blood Pressure, Cell Line, Haplotypes, Humans, Polymorphism, Single Nucleotide, Protein Isoforms, Receptors, Glucocorticoid

CONTEXT: The glucocorticoid receptor (GR) is a key hormone in the hypothalamus-pituitary-adrenal axis that regulates many pathways including blood pressure homeostasis. Thus, GR gene variation may influence interindividual differences in blood pressure in human populations.OBJECTIVE: We resequenced individual GR alleles for comprehensive discovery of GR variants and their chromosomal phase in three major American ethnic groups. We examined the influence of GR variants on blood pressure in large numbers of families using family-based association methods.DESIGN AND PARTICIPANTS: For association studies, we genotyped GR variants in family members from the Genetic Epidemiology Network of Arteriopathy (GENOA) study that were measured for multiple blood pressure traits. The GENOA families consisted of African-Americans, Mexican-Americans, and European-Americans.MAIN MEASUREMENTS: The blood pressure measurements for association studies included systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure.RESULTS: Single-nucleotide polymorphisms (SNPs) identified by resequencing were tested for associations with blood pressure measures in GENOA families. Analysis of individual SNPs identified significant associations of rs6198 A/G in exon 9beta with multiple blood pressure measures in European-Americans. Analysis of GR haplotypes found significant associations of a haplotype that is distinguished by rs6198 A/G.CONCLUSIONS: Significant associations of blood pressure with rs6198 A/G likely reflect allelic effects on GR signaling. This SNP disrupts a 3' untranslated region sequence element in exon 9beta that destabilizes mRNA, resulting in increased production of the inactive GRbeta isoform. Excess heterodimerization with the active GRalpha isoform may reduce GR signaling with subsequent physiological effects on blood pressure regulation.

Alternate JournalJ Clin Endocrinol Metab
PubMed ID18854398
PubMed Central IDPMC2630865
Grant ListHL54505 / HL / NHLBI NIH HHS / United States
R01 HL039107 / HL / NHLBI NIH HHS / United States
HL051021 / HL / NHLBI NIH HHS / United States
HL039107 / HL / NHLBI NIH HHS / United States
P01 HD047609 / HD / NICHD NIH HHS / United States
HD047609 / HD / NICHD NIH HHS / United States
U10 HL054457 / HL / NHLBI NIH HHS / United States
U01 HL054457 / HL / NHLBI NIH HHS / United States
HL054457 / HL / NHLBI NIH HHS / United States
R37 HL051021 / HL / NHLBI NIH HHS / United States

Similar Publications

Rhie A, Nurk S, Cechova M, Hoyt SJ, Taylor DJ, Altemose N, et al.. The complete sequence of a human Y chromosome. Nature. 2023;621(7978):344-354.
Saengboonmee C, Sorin S, Sangkhamanon S, Chomphoo S, Indramanee S, Seubwai W, et al.. γ-aminobutyric acid B2 receptor: A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus. World J Gastroenterol. 2023;29(28):4416-4432.
Chen F, Zhang Y, Chandrashekar DS, Varambally S, Creighton CJ. Global impact of somatic structural variation on the cancer proteome. Nat Commun. 2023;14(1):5637.
Wojcik MH, Reuter CM, Marwaha S, Mahmoud M, Duyzend MH, Barseghyan H, et al.. Beyond the exome: What's next in diagnostic testing for Mendelian conditions. Am J Hum Genet. 2023;110(8):1229-1248.
Chin C-S, Behera S, Khalak A, Sedlazeck FJ, Sudmant PH, Wagner J, et al.. Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes. Nat Methods. 2023;20(8):1213-1221.
Walker KA, Chen J, Shi L, Yang Y, Fornage M, Zhou L, et al.. Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life. Sci Transl Med. 2023;15(705):eadf5681.
Zhao N, Teles F, Lu J, Koestler DC, Beck J, Boerwinkle E, et al.. Epigenome-wide association study using peripheral blood leukocytes identifies genomic regions associated with periodontal disease and edentulism in the Atherosclerosis Risk in Communities study. J Clin Periodontol. 2023;50(9):1140-1153.
Harris RA, McAllister JM, Strauss JF. Single-Cell RNA-Seq Identifies Pathways and Genes Contributing to the Hyperandrogenemia Associated with Polycystic Ovary Syndrome. Int J Mol Sci. 2023;24(13).
Qian X, Srinivasan T, He J, Chen R. The Role of Ceramide in Inherited Retinal Disease Pathology. Adv Exp Med Biol. 2023;1415:303-307.
Calame DG, Guo T, Wang C, Garrett L, Jolly A, Dawood M, et al.. Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease. Am J Hum Genet. 2023;110(8):1394-1413.