title: Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients.
abstract: Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON). We analyzed the mitochondrial DNA (mtDNA) variation of 304 Chinese patients with m.11778G>A (sample #1) and of 843 suspected LHON patients who lack the three primary mutations (sample #2) to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3). The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10(-17), OR = 0.051, 95% CI: 0.016-0.162; #1 vs. #2, P-value = 4.44×10(-17), OR = 0.049, 95% CI: 0.015-0.154; in both cases, adjusted P-value <10(-5)) and higher frequencies of M7b (#1 vs. #3, adjusted P-value = 0.001 and #1 vs. #2, adjusted P-value = 0.004). Our result shows that mtDNA background affects LHON in Chinese patients with m.11778G>A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor.
authors: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, China.
authors: A-Mei
authors: AM
authors: Zhang
authors: Xiaoyun
authors: X
authors: Jia
authors: Rui
authors: R
authors: Bi
authors: Antonio
authors: A
authors: Salas
authors: Shiqiang
authors: S
authors: Li
authors: Xueshan
authors: X
authors: Xiao
authors: Panfeng
authors: P
authors: Wang
authors: Xiangming
authors: X
authors: Guo
authors: Qing-Peng
authors: QP
authors: Kong
authors: Qingjiong
authors: Q
authors: Zhang
authors: Yong-Gang
authors: YG
authors: Yao
mesh_terms: D044466:Asian People / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D054629:Genome, Mitochondrial / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial