X Chromosome Inactivation in Women with Alcoholism
Article first published online: 29 FEB 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 36, Issue 8, pages 1325–1329, August 2012
How to Cite
Manzardo, A. M., Henkhaus, R., Hidaka, B., Penick, E. C., Poje, A. B. and Butler, M. G. (2012), X Chromosome Inactivation in Women with Alcoholism. Alcoholism: Clinical and Experimental Research, 36: 1325–1329. doi: 10.1111/j.1530-0277.2012.01740.x
- Issue published online: 1 AUG 2012
- Article first published online: 29 FEB 2012
- Manuscript Accepted: 9 DEC 2011
- Manuscript Received: 13 JUN 2011
- Hubert & Richard Hanlon Trust. Grant Numbers: NICHD HD02528, NIAAA K01-AA015935
- X Chromosome Inactivation;
- Androgen Receptor Gene
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.
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%).
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 (χ2 test = 0.14, 2 df, p = 0.93).
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.