A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism
Received 7 January 2007; received in revised form 14 May 2007; accepted 14 May 2007. published online 03 September 2007.
Objective
To assess the association between transsexualism and allele and genotype frequencies of the common cytochrome P450 (CYP) 17 −34 T>C single nucleotide polymorphism (SNP).
Design
Case-control study.
Setting
Academic research institution.
Patient(s)
102 male-to-female (MtF) and 49 female-to-male (FtM) transsexuals, 756 male controls, and 915 female controls.
Intervention(s)
Buccal swabs and multiplex polymerase chain reaction on a microarray system.
Main Outcome Measure(s)
Analysis of the CYP17 −34 T>C SNP.
Result(s)
CYP17 −34 T>C SNP allele frequencies were statistically significantly different between FtM transsexuals and female controls (CYP17 T: 55/98 [56%] and CYP17 C: 43/98 [44%] versus CYP17 T: 1253/1826 [69%] and CYP17 C: 573/1826 [31%], respectively). In accordance, genotype distributions were also different between FtM transsexuals and female controls using a recessive genotype model (CYP17 T/T+T/C: 39/49 [80%] and C/C 10/49 [20%] vs. CYP17 T/T+T/C: 821/913 [90%] and C/C 92/913 [10%], respectively). The CYP17 −34 T>C allele and genotype distributions were not statistically significantly different between MtF transsexuals and male controls. Of note, the CYP17 −34 T>C allele distribution was gender-specific among controls (CYP17 C: males; 604 of 1512 [40%] vs. females; 573 of 1826 [31%]). The MtF transsexuals had an allele distribution equivalent to male controls, whereas FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls.
Conclusion(s)
These data support CYP17 as a candidate gene of FtM transsexualism and indicate that loss of a female-specific CYP17 T −34C allele distribution pattern is associated with FtM transsexualism.
aDepartment of Gynecologic Endocrinology and Reproductive Medicine, Medical University Vienna, Vienna, Austria
bDepartment of Obstetrics and Gynecology, Medical University Vienna, Vienna, Austria
Reprint requests: Clemens Tempfer, M.D., Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna/Austria (FAX: +43-1-40400-2911).
ABSTRACT