pattismith
Senior Member
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Bipolar disorder and 1513A>C P2RX7 polymorphism frequency
Highlights
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BD patients presents a decrease in 1513C allele frequency compared to controls.
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BD patients has a potential increase in 1513 A A and in 1513 A A/AC genotype frequency.
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BD patients presents a state of disadvantage of pro-inflammatory receptor activity.
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P2 × 7R is a possible important mediator to the pathophysiology of bipolar disorder.
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P2 × 7R is a potential biomarker for prediction and diagnosis of BD.
Abstract
Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls.
Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls.
In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder.
Sex-specific effects of gain-of-function P2RX7 variation on bipolar disorder
Highlights
•
rs1621388 and rs2230912 in P2RX7 were associated with bipolar disorder in females.
•
These P2RX7 variants were not associated with bipolar disorder in males.
•
P2RX7 variants were not associated with rapid cycling.
Abstract
Background
Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder.
Methods
We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset.
Results
P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males.
Neither P2RX7 variants associated with rapid cycling among bipolar patients.
Limitations
Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available.
Conclusion
The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects.
Highlights
•
BD patients presents a decrease in 1513C allele frequency compared to controls.
•
BD patients has a potential increase in 1513 A A and in 1513 A A/AC genotype frequency.
•
BD patients presents a state of disadvantage of pro-inflammatory receptor activity.
•
P2 × 7R is a possible important mediator to the pathophysiology of bipolar disorder.
•
P2 × 7R is a potential biomarker for prediction and diagnosis of BD.
Abstract
Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls.
Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls.
In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder.
Sex-specific effects of gain-of-function P2RX7 variation on bipolar disorder
Highlights
•
rs1621388 and rs2230912 in P2RX7 were associated with bipolar disorder in females.
•
These P2RX7 variants were not associated with bipolar disorder in males.
•
P2RX7 variants were not associated with rapid cycling.
Abstract
Background
Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder.
Methods
We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset.
Results
P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males.
Neither P2RX7 variants associated with rapid cycling among bipolar patients.
Limitations
Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available.
Conclusion
The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects.