Abstract
BackgroundMitochondrial DNA (mtDNA) copy number has been found associated with multiple diseases, including cancers, diabetes and so on. Both environmental and genetic factors could affect the copy number of mtDNA. However, limited study was available about the relationship between genetic variants and mtDNA copy number. What’s more, most of previous studies considered only environmental or genetic factors. Therefore, it’s necessary to explore the genetic effects on mtDNA copy number with the consideration of PM2.5 exposure and smoking.ResultsA multi-center population-based study was performed with 301 subjects from Zhuhai, Wuhan and Tianjin. Personal 24-h PM2.5 exposure levels, smoking and mtDNA copy number were evaluated. The Illumina Human Exome BeadChip, which contained 241,305 single nucleotide variants, was used for genotyping. The association analysis was conducted in each city and meta-analysis was adopted to combine the overall effect among three cities. Seven SNPs showed significant association with mtDNA copy number with P value less than 1.00E-04 after meta-analysis. The following joint analysis of our identified SNPs showed a significant allele-dosage association between the number of variants and mtDNA copy number (P = 5.02 × 10− 17). Further, 11 genes were identified associated with mtDNA copy number using gene-based analysis with a P value less than 0.01.ConclusionThis study was the first attempt to evaluate the genetic effects on mtDNA copy number with the consideration of personal PM2.5 exposure level. Our findings could provide more evidences that genetic variants played important roles in modulating the copy number of mtDNA.
Highlights
Mitochondrial DNA copy number has been found associated with multiple diseases, including cancers, diabetes and so on
Association between smoking, PM2.5 exposure level and Mitochondrial DNA (mtDNA) copy number In this study, we evaluated the effect of smoking and PM2.5 exposure on mtDNA copy number
We divided these subjects into high PM2.5 exposure subgroup and low PM2.5 exposure subgroup in each city based on the median PM2.5 exposure level
Summary
Mitochondrial DNA (mtDNA) copy number has been found associated with multiple diseases, including cancers, diabetes and so on. Both environmental and genetic factors could affect the copy number of mtDNA. Previous studies suggested that high PM2.5 exposure was associated with decreased mtDNA copy number [12, 13]. In 2014, Lopez and colleagues performed the first genome-wide association study (GWAS) of mtDNA copy number and identified 15 significant SNPs using 386 subjects from Spanish [17]. The environmental factors (such as PM2.5 exposure level and smoking) were not considered in previous study and these genetic variants only explained a small fraction of the total variation. More efforts are warranted to evaluate the association between genetic variants and mtDNA copy number in Chinese population
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