A genetic match between a mother and fetus may actually increase risk of
UCLA scientists have discovered that daughters who have a specific
immune-system gene that too closely matches their mothers' are more likely to
develop schizophrenia later in life.
Normally, it's a good thing when the genes in question match: after all,
they are responsible for the body's ability to “identify
The team of researchers, led by Christina Palmer, Ph.D., an associate
professor of psychiatry and human genetics at UCLA, focused on HLA-B, one of a
family of genes called the human leukocyte antigen (HLA) complex. HLA helps
the immune system distinguish the body's own proteins from those made by
foreign invaders, such as viruses and bacteria.
The report appeared in the October American Journal of Human
Genetics. The study was funded by the National Institute of Mental
Health, the Center of Excellence in Disease Genetics of the Academy of
Finland, and the University of Helsinki's Biocentrum-Helsinki research
The researchers studied a group of 274 Finnish families in which at least
one child had been diagnosed with schizophrenia or a related psychosis. Within
this group, 484 offspring had been diagnosed with schizophrenia,
schizoaffective disorder, or schizophrenia spectrum disorders. Subjects were
born between 1940 and 1976.
The scientists drew blood samples from those with schizophrenia and all
available family members, including siblings and parents. DNA analysis was
then used to identify families in which the children's HLA-B gene closely
matched their mothers' and those in which the HLA-B genes were mismatched.
Analysis of the entire sample revealed that daughters whose HLA-B gene
matched their mothers' were 1.7 times more likely to develop schizophrenia
than children whose gene didn't match their mothers'. The researchers then
calculated that if this genetic risk due to matching could have been avoided
(for example, through genetic counseling), up to 12 percent of the cases of
schizophrenia in daughters could have been prevented.
In fact, determining a patient's HLA gene makeup is routinely used to
assess clinical risks, and that process is commonly known as “tissue
typing.” Because the HLA complex controls the immune system's“
recognition of self,” HLA typing of a transplant recipient must
closely match the HLA gene typing of donated organ tissue. If a donated
organ's HLA complex contains a high number of individual genes not found in
the recipient, the risk of rejection increases dramatically.
“Normally, the body would reject a [transplanted] organ that isn't
the same HLA typing as self, but for reasons that are not well understood, a
mother's body does not reject a fetus when that fetus is of a different HLA
typing,” explained Palmer, who is also a staff researcher at the Semel
Institute for Neuroscience and Human Behavior.
“It seems pretty clear that it's a good thing for the HLA genes of a
mother and her fetus to not match,” she added. “We suspect that
HLA matching increases a woman's susceptibility to pregnancy complications,
which in turn predisposes her child to schizophrenia. This is one more piece
in the puzzle of identifying genetic markers for the disease.”
“Our current findings clearly suggest that schizophrenia risk rises,
especially in daughters, when the child's HLA-B gene too closely matches its
mother's,” Palmer told Psychiatric News. “We don't know
whether sons who match are not affected, or maybe sons are affected and are so
compromised that they are less likely to come to term.”
“In the future, we also may be able to produce tailored risk
assessments for individuals with personal or family histories of
schizophrenia,” said Palmer.
An abstract of “HLA-B Maternal-Fetal Genotype Matching
Increases Risk of Schizophrenia” is posted at<www.journals.uchicago.edu/AJHG/journal/issues/v79n4/43692/brief/43692.abstract.html>.▪