Does EDAR Gene Affect Meibomian Glands Development in Human?

Abstract

 

Purpose

 

EDAR gene plays an important role in the development of hair,teeth and other ectodermal derivatives. Asian-specific mutation in derived EDAR allele was found associated with enlargement of meibomian glands(MGs) in mouse. This study was conducted to test the hypothesis that EDAR contributes to population differentiation regarding MG morphology.

 

Methods

 

The derived EDAR allele attained high frequency in East Asian and moderate in Uygur, absent in European. We recruited 37 unrelated individuals and divided them into 3 groups according to ethnicity (Chinese(Ch):17; Uygur(Uy):13; Europeans(Eu):7). DNA was extracted from blood samples for genotyping. MG morphology was observed by laser scanning confocal microscopy(LSCM) in vivo, we measured glandular acinar unit density(MGAUD) and acinar longest/shortest diameter(MGALD/MGASD) as main parameters for comparative analysis to investigate the association of genotype and phenotype.

 

Results

 

We designed primers to genotype EDAR V370A polymorphism (rs3827760), the allele frequency was consistent with expectations under Hardy-Weinberg equilibrium,as reported previously. LSCM demonstrated that MGASD was significantly smaller in Ch(31.6±7.5μm)compared with Uy(43.2±21.6μm;p=0.0368, Mann-Whitney U test) and Eu(48.0±19.2μm;p=0.0252). However, values of MGAUD(Ch:114.6±28.0/mm²; Uy:111.0±39.5/mm²; Eu:117.8±35.6/mm²) and MGALD(Ch:89.5±13.0μm; Uy:82.7±19.5μm; Eu:82.5±14.5μm) had no significant differences (p>0.05) among populations. In order to study the relation between genotype and phenotype, we performed both additive and dominant gene model then did linear regression analysis, results of which indicated that EDAR V370A was not correlated with MG density and diameter(p>0.05,Spearman).

 

Conclusions

 

Genotyping revealed that difference of derived EDAR allele frequency did exist among populations. Based on limited phenotype data provided by LSCM, we didn’t demonstrate the impact of population difference on MG morphological pattern, no association was found between genotype and phenotype. Due to small sample size and other reasons, we didn't get outcomes consistent with those in previous animal experiments. Further population-based association studies need to be carried out to unequivocally test our hypothesis and reach a definite conclusion.

 

 

FIGURE 1. Meibomian glandular acinar units imaged by LSCM. (A)Chinese; (B)Uyghur;(C)European.

 

 

TABLE 1. Correlation between EDAR V370A and MGs

 

Keywords: 596 microscopy: confocal/tunneling • 440 candidate gene analysis