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 chi(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: chi(2)=37.17, p=2.45x10(-5); DXS984: chi(2)=33.88, p=1.66x10(-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.