Evaluation of the X-linked modifier loci for Leber hereditary optic neuropathy with the G11778A mutation in Chinese

PURPOSE: To test the association of the X-chromosome regions (Xp21.1–q21.2 and Xq25–27.2) with Leber hereditary optic neuropathy (LHON) in Chinese patients. METHODS: One hundred and seventy-five male LHON patients with the G11778A mutation and 100 unrelated normal males participated. Twelve microsatellite markers and four single-nucleotide polymorphisms (SNPs) were genotyped for patients and controls. A χ(2) or Fisher’s exact test was used to compare the frequencies of genotypes as well as haplotypes in the two groups. RESULTS: Significant differences between patients and controls were found in two isolated microsatellite markers (DXS6803: χ(2)=37.17, p=2.45×10(−5); DXS984: χ(2)=33.88, p=1.66×10(−6)) based on genotype frequencies. However, no significant differences for genotype and haplotype frequencies were found in the other 14 markers located in the two reported regions of Xp21.1–q21.2 and Xq25–27.2. CONCLUSIONS: Our results provide suggestive evidence of X-linked modifiers on the expression of LHON. Further studies are needed to identify the exact nuclear genes that might affect LHON expression.