AUTHOR=Jiang Heng , Yan Bin , Meng Zhishang , Zhang Lusi , Lei Hetian , Luo Jing 

TITLE=The MDM2 Single-Nucleotide Polymorphism T309G Is Associated With the Development of Epimacular Membranes

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.841660

DOI=10.3389/fcell.2022.841660

ISSN=2296-634X

ABSTRACT=<p><bold><italic>Purpose:</italic></bold> To investigate the role of the <italic>mouse double minute 2</italic> (<italic>MDM2</italic>) gene single-nucleotide polymorphism (SNP) T309G in the development of epimacular membranes (EMMs) by analyzing the genotype distribution and consistency of the polymorphism in paired membrane-blood samples.</p><p><bold><italic>Methods:</italic></bold> This was a cross–sectional genetic association study of patients with proliferative vitreoretinopathy (PVR) or EMMs. PVR membranes (PVRMs), internal limiting membranes (ILMs) (PVR-ILMs) and blood samples (PVR-blood) from patients with PVR, and EMMs, EMM-ILMs and EMM-blood from patients with EMMs were collected. The genotype of all samples was determined by Sanger sequencing. Sex composition, mean age, the genotype distribution of <italic>MDM2</italic> T309G, the allelic frequency of the <italic>MDM2</italic> SNP309 G allele (% G) and the somatic mutation rate at the <italic>MDM2</italic> T309G locus (% M) were analyzed and compared. The PVR and healthy Chinese donor groups were used as controls for different comparisons.</p><p><bold><italic>Results:</italic></bold> The EMM group of 62 patients was older than the PVR group of 61 patients by an average of 8.87 years (<italic>p</italic> &lt; 0.0001), but the two groups were statistically similar in the sex composition (<italic>p</italic> = 0.1754). Importantly, G allele carriers were at a higher risk of developing EMMs than non-G allele carriers (<italic>p</italic> = 0.0479; OR = 2.047). Moreover, EMM-blood exhibited a significantly higher % G than blood samples from healthy Chinese donors (EMM-blood: 56.78%, donors: 45.61%; <italic>p</italic> = 0.0256; OR = 1.567). Regarding membrane-blood consistency, % M was significantly different between PVRMs and EMMs (PVRMs: 2.63%, EMMs: 21.57%; <italic>p</italic> = 0.0097; OR = 10.18) but not between different types of ILMs (PVR-ILMs: 18.18%, EMM-ILMs: 29.17%; <italic>p</italic> = 0.6855). Furthermore, EMMs (<italic>p</italic> = 0.0053; OR = 8.250) and EMM-ILMs (<italic>p</italic> = 0.0233; OR = 14.40) from patients with preoperative macular holes were more predisposed toward somatic mutations at the <italic>MDM2</italic> T309G locus than those from patients without preoperative macular holes.</p><p><bold><italic>Conclusions:</italic></bold><italic>MDM2</italic> T309G is associated with the development of EMMs. Herein, the <italic>MDM2</italic> SNP309 G allele is first reported as an associated factor of EMMs in a Chinese population. In addition, EMMs and ILMs are genetically unstable at the <italic>MDM2</italic> T309G locus, especially when complicated with preoperative macular holes.</p>