SLR - September 2020 - Victoria R. Knauf

Association of Estrogen Receptor ß Polymorphisms with Posterior Tibial Tendon Dysfunction

Reference: Nogara, PRB, Godoy-Santos, AL, Fonseca, FCP, Cesar-Netto C, Carvalho KC, Baracat EC, Maffulli N, Pontin PA, Santos MCL. Association of Estrogen Receptor ß Polymorphisms with Posterior Tibial Tendon Dysfunction. Journal of Molecular and Cellular Biochemistry. 2020 May; 471:63–69.

Scientific Literature Review

Reviewed By: Victoria R. Knauf, DPM
Residency Program: Jackson South Medical Center - Miami, FL 

Podiatric Relevance: Posterior tibial tendon dysfunction (PTTD), a common and primary contributor to adult acquired flatfoot, is three-fold more common in women than men. This persistent pain to the plantar medial arch of the foot is caused by degeneration of healthy posterior tibial tendon secondary to intrinsic and extrinsic factors. Understanding and recognizing intrinsic factors and etiology of PTTD is important for understanding and treating this pathology for optimal patient treatment outcomes. 

Methods: This is a case-controlled cross sectional study consists of 400 patients from outpatient clinics in Brazil to investigate the association of single nucleotide polymorphisms (SNP) of estrogen receptor-beta gene, specifically rs4986938 and rs1256049, with Johnson and Strom Stage II or III  PTTD. Patients diagnosed with and without PTTD were then further broken down into men, postmenopausal women, and premenopausal women to assess the role of estrogen SNPs in PTTD. Polymerase chain reaction from epithelial buccal cells was performed in all groups to determine frequency of alleles and genotypes in premenopause group, postmenopause group, and men with and without PTTD. 

Results: Statistical analysis utilizing Chi-square test and Hardy–Weinberg equilibrium showed a significant difference in ER-ß SNP rs4986938 (p=0.045) between experimental and control groups, including experimental groups postmenopausal women and only men groups, showing an association between this allele and PTTD (p<0.0001). However no significant difference between groups of premenopausal women or with the ER -ß SNPs rs1256049 frequency of alleles and genotypes (p>0.05) were noted.

Conclusions: The study suggests SNP of estrogen-receptor beta rs4986938 may be a contributing intrinsic factor to degeneration of the posterior tibial tendon in the studied population. It was also noted this genetic factor could be a determinant for PTTD in men. Limitations in this study include population. Although 400 participants were included in study, all participants were from the southeast region of Brazil. A large genetic component from the same region could be creating a false positive correlation between the estrogen gene and PTTD that may not resemble another population to be studied. There is still much to investigate regarding specific intrinsic factors and additional extrinsic factors that could alter the morphology of the tendon to ultimately create symptomatic PTTD. Higher levels of research are needed to ultimately evaluate intrinsic and extrinsic factors contributing to PTTD.

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