UNASSIGNED: The mtDNA was sequenced from age- and sex-matched study groups, being high tension glaucoma (HTG, n=71), normal tension glaucoma patients (NTG, n=33), ocular hypertensive subjects (OH, n=7), and cataract controls (without glaucoma; n=30), all without remarkable comorbidities.
UNASSIGNED: No association was found between the number of mtDNA variants in genes encoding proteins, tRNAs, rRNAs, and in non-coding regions in the different study groups. Next, variants that controls shared with the other groups were discarded. A significantly higher number of exclusive variants was observed in the D-loop region for the HTG group (~1.23 variants/subject), in contrast to controls (~0.35 variants/subject). In the D-loop, specifically in the 7S DNA sub-region within the Hypervariable region 1 (HV1), we found that 42% of the HTG and 27% of the NTG subjects presented variants, while this was only 14% for the controls and OH subjects. As we have previously reported a reduction in mtDNA copy number in HTG, we analysed if specific D-loop variants could explain this. While the majority of glaucoma patients with the exclusive D-loop variants m.72T>C, m.16163 A>G, m.16186C>T, m.16298T>C, and m.16390G>A presented a mtDNA copy number below controls median, no significant association between these variants and low copy number was found and their possible negative role in mtDNA replication remains uncertain. Approximately 38% of the HTG patients with reduced copy number did not carry any exclusive D-loop or other mtDNA variants, which indicates that variants in nuclear-encoded mitochondrial genes, environmental factors, or aging might be involved in those cases.
UNASSIGNED: In conclusion, we found that variants in the D-loop region may be a risk factor in a subgroup of POAG, possibly by affecting mtDNA replication.
■对年龄和性别匹配的研究组的mtDNA进行测序,是高眼压青光眼(HTG,n=71),正常眼压性青光眼患者(NTG,n=33),眼高血压受试者(OH,n=7),和白内障对照(无青光眼;n=30),都没有明显的合并症。
■编码蛋白质的基因中mtDNA变体的数量之间没有发现关联,tRNAs,rRNAs,以及不同研究组的非编码区域。接下来,与其他组共享的对照变体被丢弃.在HTG组的D-loop区域中观察到明显更多的专有变体(〜1.23变体/受试者),与对照(~0.35个变体/受试者)相反。在D循环中,特别是在高变区1(HV1)内的7SDNA亚区,我们发现42%的HTG和27%的NTG受试者呈现变异,而对照组和OH受试者的这一比例仅为14%。正如我们之前报道的HTG中mtDNA拷贝数的减少,我们分析了特定的D环变异是否可以解释这一点.虽然大多数青光眼患者具有独特的D-loop变异m.72T>C,m.16163A>G,m.16186C>T,m.16298T>C,m.16390G>A显示mtDNA拷贝数低于对照中位数,未发现这些变异与低拷贝数之间存在显著关联,它们在mtDNA复制中可能的负作用仍不确定.大约38%的HTG患者的拷贝数减少没有携带任何专有的D-loop或其他mtDNA变体,这表明核编码线粒体基因的变异,环境因素,或者在这些情况下可能涉及衰老。
■总而言之,我们发现D-loop区域的变异可能是POAG亚组的危险因素,可能通过影响mtDNA复制。