Abstract
To investigate whether mitochondrial DNA haplogroups M or N are related to occurrence or manifestations of systemic lupus erythematosus (SLE), we collected M/N haplogrouping and clinical characteristics from 868 Han Chinese women with SLE, as well as for 870 age-matched healthy Han Chinese control women. M/N haplogroups were determined in all subjects using allele-specific amplification. The frequency of M haplogroup in all patients was 429 (49.4%) and the frequency of N haplogroup, 439 (50.6%). The corresponding frequencies in controls were 456 (52.4%) and 414 (47.6%) (P = 0.213). Among women older than 50 years at onset age, the N haplogroup was significantly higher in patients than in healthy controls (59.6% vs 41.7%, P = 0.042). The N haplogroup was associated with significantly higher risk for certain SLE characteristics: hematological system damage (OR 2.128, 95%CI 1.610 to 2.813), skin impairment (OR 1.873, 95%CI 1.428 to 2.457), neurological disturbance (OR 3.956, 95%CI 1.874 to 8.352) and alopecia (OR 1.322, 95%CI 1.007 to 1.737 ). Our results suggest that in Han Chinese women, the mtDNA N haplogroup is associated with higher risk of late-onset SLE, skin impairment, neurological disturbance, hematological system damage and alopecia.
Highlights
Polymorphisms in mitochondrial DNA, a 16.6-kbp double-stranded molecule encoding several rRNAs, tRNAs and proteins[1], have been linked to risk of several complex diseases, including diabetes mellitus, cancer, and Parkinson’s2
Given a US study suggesting that specific mitochondrial DNA (mtDNA) single-nucleotide polymorphisms (SNPs) haplogroups may affect risk of breast cancer in women[3], researchers have already focused genetic factors relating systemic lupus erythematosus (SLE) on SNP and on SNP linkage haplotypes like Toll-like receptors[14]
We show here for the first time that there is an association between mtDNA M/N haplogroups and risk of SLE in Han Chinese women
Summary
Polymorphisms in mitochondrial DNA (mtDNA), a 16.6-kbp double-stranded molecule encoding several rRNAs, tRNAs and proteins[1], have been linked to risk of several complex diseases, including diabetes mellitus, cancer, and Parkinson’s2. When multiple single-nucleotide polymorphisms (SNPs) occur together as part of an mtDNA haplotype, oxidative respiratory chain activity can be affected, disturbing the ratio of production of ATP to reactive oxygen species (ROS). Ethnic and regional genetic heterogeneity may reduce the reliability of SLE studies based on SNPs, including GWAS. This is similar to the case in diabetes research, where GWAS have reported conflicting results for the same disease susceptibility gene candidates[12,13]. Given a US study suggesting that specific mtDNA SNP haplogroups may affect risk of breast cancer in women[3], researchers have already focused genetic factors relating SLE on SNP and on SNP linkage haplotypes like Toll-like receptors[14]. Most Europeans carry sequences for these and other SNPs that are collectively denominated as haplogroup N, while Han Chinese carry haplogroups N and M [searching from mtDNA database]
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