Polymorphisms of STAT4 gene in the pathogenesis of endometriosis

STAT4 gene polymorphisms and endometriosis?

Key Points

Highlight:

• Dr. Barbosa group suggest that STAT4 polymorphisms can influence the pathogenesis of endometriosis based on their recent case-control study.

Background:

• Numerous pieces of evidence indicate that immunological alterations influence women's susceptibility to endometriosis.
• The signal transducer and activator of transcription 4 (STAT4) is a member of the Janus kinase-STAT pathway and plays a central role in interferon signaling which is related to immunological processes.
• Therefore, any change in activity or expression of STAT can alter the immune system's function and response.
• Recently, Zamani et al. found a significant association between STAT4 rs7582694 polymorphism and susceptibility to endometriosis-related infertility in Iranian women.
• Based on the previous finding, Dr. Barbosa group from Brazil aim to evaluate whether the STAT4 polymorphisms (rs7582694, rs7574865, rs7601754, and rs11889341) are associated with the pathogenesis of endometriosis in Brazilian women.

Key points:

• This study sample was comprised of 238 women with endometriosis and 201 healthy, fertile women without endometriosis.
• A single-polymorphism analysis revealed that the TT genotype of the rs7574865/T > G polymorphism was significantly frequent in women with minimal or mild endometriosis than in the controls.
• The CGAC, GTAT, and GTAC haplotypes more frequently occurred in infertile women with endometriosis than in the controls.
• In addition, the CGAC haplotype was more frequently found in those with minimal or mild endometriosis than in the controls.
• No difference was observed regarding the endometriosis stage.

Conclusions and limitations:

• Collectively, Dr. Barbosa group suggest that STAT4 polymorphisms can influence the pathogenesis of endometriosis.
• However, further studies are required to have a better understanding; including the functional role of these polymorphisms, investigating more various STAT4 single-nucleotide polymorphisms, and increasing the number of participated patients.   

Lay Summary

Endometriosis is one of the most common gynecological diseases in reproductive-age women characterized by the occurrence of endometrial tissue outside the uterine cavity. Researchers have put forward numerous hypotheses to explain ectopic endometrial tissue, and the bulk of the evidence indicates that immunological alterations influence women's susceptibility to endometriosis.

The signal transducer and activator of transcription 4 (STAT4) is a member of the Janus kinase-STAT pathway and plays a central role in interferon signaling which is related to immunological processes. As STAT4 is a critical mediator of the immune response, any change in its activity or expression can alter the immune system's function and response.

Recently, Zamani et al. found a significant association between STAT4 rs7582694 polymorphism and susceptibility to endometriosis-related infertility in Iranian women. Based on this finding, Dr. Barbosa group from Brazil aim to evaluate whether the STAT4 polymorphisms were associated with the pathogenesis of endometriosis in Brazilian women.

238 women with endometriosis and 201 healthy women have participated in this study. There was no difference in genotype frequencies for the rs7582694/C>G polymorphism between the endometriosis group and the control group.

However, a single-polymorphism analysis revealed that the TT genotype of the rs7574865/T > G polymorphism was significantly more frequent in women with minimal or mild endometriosis than in the controls. The CGAC, GTAT, and GTAC haplotypes more frequently occurred in infertile women with endometriosis than in the controls. In addition, the CGAC haplotype was more frequently found in those with minimal or mild endometriosis than in the controls. No difference was observed regarding the endometriosis stage.

In conclusion, Dr. Barbosa group suggest that STAT4 polymorphisms can influence the pathogenesis of endometriosis. However, further studies are required to have a better understanding; including the functional role of these polymorphisms, investigating more various STAT4 single-nucleotide polymorphisms, and increasing the number of participated patients.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/30887509