GST gene polymorphisms linked to early-onset bipolar disorder
MedWire News: Polymorphisms in genes encoding glutathione S-transferase (GST) detoxification enzymes modify risk for developing early-onset bipolar disorder, study results show.
However, interactions between GST isoenzymes appear to be complex and larger studies will be needed to elucidate mechanisms of susceptibility, say Mostafa Saadat (Shiraz University, Iran) and colleagues in the journal Psychiatry Research.
Free radicals and reactive oxygen species (ROS) can cause oxidative cell injury if not effectively eliminated by enzymatic and non-enzymatic cellular defenses.
A recent study suggested that oxidative stress markers are increased in bipolar disorder and that oxidative stress may play a role in the pathophysiology of the illness.
GSTs are ubiquitous, multifunctional enzymes that play a key role in cellular detoxification, and could thus be potential candidate genes in bipolar disorder.
To investigate, the researchers genotyped for GSTM1 and GSTT1 in 228 bipolar disorder patients and 236 mentally healthy blood donors matched with the patients according to age and gender.
The GSTM1-null and GSTT1-null alleles represent deletions of the GSTM1 and GSTT1 genes, respectively, and therefore homozygosity for these alleles means no enzyme and no activity.
Saadat and colleagues report that the prevalence of the GSTM1-null genotype was 45.6% in the patient group and 53.3% in controls; while the frequency of the GSTT1-null genotype was 27.1% in patients and 27.5% in controls.
Analysis revealed that neither the GSTM1 nor GSTT1 polymorphism was associated with risk for bipolar disorder.
After stratifying the group according to age at bipolar disorder diagnosis, the researchers found that among patients with early-onset (below 19 years old) bipolar disorder, the GSTM1-null genotype was associated with a significantly decreased risk for bipolar disorder compared with the positive genotype (odds ratio [OR]=0.43).
Conversely, the GSTT1-null polymorphism was associated with an increased risk for early-onset bipolar disorder, although this was of borderline significance (OR=1.75).
Further analysis showed that a combination of GSTM1-positive and GSTT1-null genotype versus GSTM1-positive and GSTT1-positive was associated with a significantly increased risk for early-onset bipolar disorder (OR=2.28).
There was no significant association between the study polymorphisms and risk for bipolar disorder among the late-onset group.
While emphasizing the need for further studies, Saadat et al say that "the present findings indicate that GSTM1 and GSTT1 are candidate polymorphisms for susceptibility to bipolar disorder among adolescents."
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By Andrew Czyzewski