title: X chromosome inactivation in women with alcoholism.
abstract: BACKGROUND
  All female mammals with 2 X chromosomes balance gene expression with males having only 1 X by inactivating one of their X chromosomes (X chromosome inactivation [XCI]). Analysis of XCI in females offers the opportunity to investigate both X-linked genetic factors and early embryonic development that may contribute to alcoholism. Increases in the prevalence of skewing of XCI in women with alcoholism could implicate biological risk factors.
  
  
  METHODS
  The pattern of XCI was examined in DNA isolated in blood from 44 adult women meeting DSM-IV criteria for an alcohol use disorder and 45 control women with no known history of alcohol abuse or dependence. XCI status was determined by analyzing digested and undigested polymerase chain reaction (PCR) products of the polymorphic androgen receptor (AR) gene located on the X chromosome. Subjects were categorized into 3 groups based upon the degree of XCI skewness: random (50:50 to 64:36%), moderately skewed (65:35 to 80:20%), and highly skewed (>80:20%).
  
  
  RESULTS
  XCI status from informative women with alcoholism was found to be random in 59% (n = 26), moderately skewed in 27% (n = 12), or highly skewed in 14% (n = 6). Control subjects showed 60, 29, and 11%, respectively. The distribution of skewed XCI observed among women with alcoholism did not differ statistically from that of control subjects (χ(2) test = 0.14, 2 df, p = 0.93).
  
  
  CONCLUSIONS
  Our data did not support an increase in XCI skewness among women with alcoholism or implicate early developmental events associated with embryonic cell loss or unequal (nonrandom) expression of X-linked gene(s) or defects in alcoholism among women.
authors.affiliation: Department of Psychiatry, Kansas University Medical Center, Kansas City, USA. amanzardo@kumc.edu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Manzardo
authors.forename: Rebecca
authors.initials: R
authors.lastname: Henkhaus
authors.forename: Brandon
authors.initials: B
authors.lastname: Hidaka
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Penick
authors.forename: Albert B
authors.initials: AB
authors.lastname: Poje
authors.forename: Merlin G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D050172:Genes, X-Linked / Q000187:drug effects; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011944:Receptors, Androgen / Q000235:genetics; D012307:Risk Factors; D049951:X Chromosome Inactivation / Q000187:drug effects*
chemical_list: D011944:Receptors, Androgen; D004247:DNA