Ethnic variation in allele distribution of the androgen receptor (AR) (CAG) n repeat

Christine M. Ackerman, Lynn P. Lowe, Hoon Lee, M. Geoffrey Hayes, Alan R. Dyer, Boyd E. Metzger, William L. Lowe, Margrit Urbanek*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG) n repeat polymorphism in exon 1 of the AR gene is thought to regulate AR activity, with longer alleles conferring reduced receptor activity. Therefore, the evaluation of the allelic distribution of the AR (CAG) n repeat in various ethnic groups is crucial in understanding the interindividual variability in AR activity. We evaluated ethnic variation of this AR polymorphism by genotyping individuals from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome study cohort. We genotyped 4421 Caucasian mothers and 3365 offspring of European ancestry; 1494 Thai mothers and 1742 offspring; 1119 Afro-Caribbean mothers and 1142 offspring; and 780 Hispanic mothers and 770 offspring of Mexican ancestry from Bellflower, California. The distributions of (CAG) n alleles among all 4 ethnic groups are significantly different (P < .0001). Pairwise tests confirmed significant differences between each pair of ethnicities tested (P < 10 -28). The relative AR (CAG) n repeat length in the different groups was as follows: Afro-Caribbean (shortest repeat lengths and greatest predicted AR activity) < Caucasian < Hispanic < Thai (longest repeat length and lowest predicted AR activity). Significant interethnic differences in the allele frequencies of the AR exon 1 (CAG) n polymorphism exist. Our results suggest that there may be potential ethnic differences in androgenic pathway activity and androgen sensitivity.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalJournal of Andrology
Volume33
Issue number2
DOIs
StatePublished - Mar 1 2012

Fingerprint

Androgen Receptors
Alleles
Mothers
Hispanic Americans
Ethnic Groups
Exons
Codonopsis
Pregnancy Outcome
Gene Frequency
Hyperglycemia
Androgens
Pancreas
Skeletal Muscle
Homeostasis
Outcome Assessment (Health Care)
Liver

Keywords

  • HAPO
  • Polyglutamine repeat
  • Polymorphism
  • Pregnancy
  • X-linked

ASJC Scopus subject areas

  • Urology
  • Reproductive Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

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title = "Ethnic variation in allele distribution of the androgen receptor (AR) (CAG) n repeat",
abstract = "The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG) n repeat polymorphism in exon 1 of the AR gene is thought to regulate AR activity, with longer alleles conferring reduced receptor activity. Therefore, the evaluation of the allelic distribution of the AR (CAG) n repeat in various ethnic groups is crucial in understanding the interindividual variability in AR activity. We evaluated ethnic variation of this AR polymorphism by genotyping individuals from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome study cohort. We genotyped 4421 Caucasian mothers and 3365 offspring of European ancestry; 1494 Thai mothers and 1742 offspring; 1119 Afro-Caribbean mothers and 1142 offspring; and 780 Hispanic mothers and 770 offspring of Mexican ancestry from Bellflower, California. The distributions of (CAG) n alleles among all 4 ethnic groups are significantly different (P < .0001). Pairwise tests confirmed significant differences between each pair of ethnicities tested (P < 10 -28). The relative AR (CAG) n repeat length in the different groups was as follows: Afro-Caribbean (shortest repeat lengths and greatest predicted AR activity) < Caucasian < Hispanic < Thai (longest repeat length and lowest predicted AR activity). Significant interethnic differences in the allele frequencies of the AR exon 1 (CAG) n polymorphism exist. Our results suggest that there may be potential ethnic differences in androgenic pathway activity and androgen sensitivity.",
keywords = "HAPO, Polyglutamine repeat, Polymorphism, Pregnancy, X-linked",
author = "Ackerman, {Christine M.} and Lowe, {Lynn P.} and Hoon Lee and Hayes, {M. Geoffrey} and Dyer, {Alan R.} and Metzger, {Boyd E.} and Lowe, {William L.} and Margrit Urbanek",
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Ethnic variation in allele distribution of the androgen receptor (AR) (CAG) n repeat. / Ackerman, Christine M.; Lowe, Lynn P.; Lee, Hoon; Hayes, M. Geoffrey; Dyer, Alan R.; Metzger, Boyd E.; Lowe, William L.; Urbanek, Margrit.

In: Journal of Andrology, Vol. 33, No. 2, 01.03.2012, p. 210-215.

Research output: Contribution to journalArticle

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T1 - Ethnic variation in allele distribution of the androgen receptor (AR) (CAG) n repeat

AU - Ackerman, Christine M.

AU - Lowe, Lynn P.

AU - Lee, Hoon

AU - Hayes, M. Geoffrey

AU - Dyer, Alan R.

AU - Metzger, Boyd E.

AU - Lowe, William L.

AU - Urbanek, Margrit

PY - 2012/3/1

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N2 - The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG) n repeat polymorphism in exon 1 of the AR gene is thought to regulate AR activity, with longer alleles conferring reduced receptor activity. Therefore, the evaluation of the allelic distribution of the AR (CAG) n repeat in various ethnic groups is crucial in understanding the interindividual variability in AR activity. We evaluated ethnic variation of this AR polymorphism by genotyping individuals from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome study cohort. We genotyped 4421 Caucasian mothers and 3365 offspring of European ancestry; 1494 Thai mothers and 1742 offspring; 1119 Afro-Caribbean mothers and 1142 offspring; and 780 Hispanic mothers and 770 offspring of Mexican ancestry from Bellflower, California. The distributions of (CAG) n alleles among all 4 ethnic groups are significantly different (P < .0001). Pairwise tests confirmed significant differences between each pair of ethnicities tested (P < 10 -28). The relative AR (CAG) n repeat length in the different groups was as follows: Afro-Caribbean (shortest repeat lengths and greatest predicted AR activity) < Caucasian < Hispanic < Thai (longest repeat length and lowest predicted AR activity). Significant interethnic differences in the allele frequencies of the AR exon 1 (CAG) n polymorphism exist. Our results suggest that there may be potential ethnic differences in androgenic pathway activity and androgen sensitivity.

AB - The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG) n repeat polymorphism in exon 1 of the AR gene is thought to regulate AR activity, with longer alleles conferring reduced receptor activity. Therefore, the evaluation of the allelic distribution of the AR (CAG) n repeat in various ethnic groups is crucial in understanding the interindividual variability in AR activity. We evaluated ethnic variation of this AR polymorphism by genotyping individuals from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome study cohort. We genotyped 4421 Caucasian mothers and 3365 offspring of European ancestry; 1494 Thai mothers and 1742 offspring; 1119 Afro-Caribbean mothers and 1142 offspring; and 780 Hispanic mothers and 770 offspring of Mexican ancestry from Bellflower, California. The distributions of (CAG) n alleles among all 4 ethnic groups are significantly different (P < .0001). Pairwise tests confirmed significant differences between each pair of ethnicities tested (P < 10 -28). The relative AR (CAG) n repeat length in the different groups was as follows: Afro-Caribbean (shortest repeat lengths and greatest predicted AR activity) < Caucasian < Hispanic < Thai (longest repeat length and lowest predicted AR activity). Significant interethnic differences in the allele frequencies of the AR exon 1 (CAG) n polymorphism exist. Our results suggest that there may be potential ethnic differences in androgenic pathway activity and androgen sensitivity.

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