The CYP17 MspA1 Polymorphism and the Gender Dysphoria

Area of Science:

• Genetics and Endocrinology
• Human Genetics
• Molecular Biology

Background:

• The A2 allele of the CYP17 MspA1 polymorphism is associated with elevated serum levels of testosterone, progesterone, and estradiol.
• Steroid hormone levels are influenced by genetic factors, including specific gene polymorphisms.

Purpose of the Study:

• To investigate the potential association between the CYP17 MspA1 polymorphism and transsexualism.
• To explore if genetic variations in CYP17 influence gender identity.

Main Methods:

• Genotyping analysis of the CYP17 MspA1 polymorphism in a cohort of male-to-female (MtF) and female-to-male (FtM) transsexual individuals, as well as control groups.
• Polymerase chain reaction (PCR) amplification and MspA1 enzyme digestion to identify allele frequencies.
• Comparison of obtained data with the 1000 Genomes Data Base and a comprehensive MEDLINE literature search.

Main Results:

• The A2 allele frequency was significantly higher in the female-to-male (FtM) transsexual group (0.45) compared to male-to-female (MtF) transsexuals (0.36), female controls (0.38), and male controls (0.39).
• This FtM > MtF pattern in A2 allele frequency reached statistical significance (P = 0.041).
• Allele frequencies for the CYP17 MspA1 polymorphism were not found to be gender-specific in the general population (P = 0.887).

Conclusions:

• The study identified a sex-dependent allele distribution of the CYP17 MspA1 polymorphism within the transsexual population, specifically a higher prevalence in FtM individuals compared to MtF individuals.
• These findings suggest a potential, hypothetical involvement of the A2 allele in the development of transsexualism.
• General population allele frequencies for this polymorphism are primarily influenced by geographic origin and ethnic background, rather than sex.