A gene variant has been identified that appears to be associated with female-to-male transsexuality – the feeling some women have that they belong to the opposite sex.

While such complex behaviour is likely the result of multiple genes, environmental and cultural factors, the researchers say the discovery suggests that transsexuality does have a genetic component.

The variation is in the gene for an enzyme called cytochrome P17, which is involved in the metabolism of sex hormones. Its presence leads to higher than average tissue concentrations of male and female sex hormones, which may in turn influence early brain development.

Clemens Tempfer and his colleagues at the Medical University of Vienna in Austria discovered the variant after analysing DNA samples from 49 female-to-male (FtM) and 102 male-to-female (MtF) transsexuals, as well as 1669 non-transsexual controls.


The variant was more common in men than women, although it doesn’t seem to be implicated in MtF transsexuality as the proportion of MtF transsexuals with it was similar to that in non-transsexual men. In women, however, there were some differences: 44% of FtM transsexuals carried it, compared with 31% of non-transsexual women.

Testosterone boost

While there are many women with the variant who are not transsexual and many FtM transsexuals who lack it, the finding raises the possibility that the variant makes women more likely to feel that their bodies are of the wrong sex, and that this is a result of their brains having been exposed to higher than average levels of sex hormones during development.

“It may increase the likelihood that people will become transsexual,” says Tempfer. But he stresses that their cultural environment is also important.

“The present study found that a mutant gene that ultimately results in higher testosterone levels is overrepresented in female-to male transsexualism, says Mikael Landén of the Karolinska Institute in Stockholm, Sweden.

“This is in line with what we previously know about masculinisation of the brain and is therefore less likely to be a chance finding”, he says. “Hence, the study is important and adds to the notion that gender identity is influenced by sex hormones early in life, and that certain gene combinations make individuals more vulnerable to aberrant effects.”

Motive fears

However, Janett Scott, former president of the Beaumont Society, a UK support group for transgender people, is concerned that positing a biological basis for transsexuality may encourage people to try and cure it.

“Nature may have made us the way that we are, but nurture is what gives us a problem,” she says.

Tempfer strongly denies any such motive for his research: “That is completely out of the question,” he says.

Nonetheless, he says, if other gene variants with a stronger association to transsexuality are identified, establishing a diagnosis might become easier. This might allow gender reassignment surgery or hormone therapy to start earlier in life.

Journal reference: Fertility and Sterility (DOI: 10.1016/j.fertnstert.2007.05.056)

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