Mitochondrial DNA copy number, but not haplogroup, confers a genetic susceptibility to leprosy in Han Chinese from Southwest China.
BACKGROUND
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA) background and mtDNA copy number.


METHODS
We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls) and 12 leprosy patients upon diagnosis.


RESULTS
Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008). Past medical treatments had no effect on the alteration of mtDNA copy number.


CONCLUSIONS
Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Dong
D
Wang
Ling-Yan
LY
Su
A-Mei
AM
Zhang
Yu-Ye
YY
Li
Xiao-An
XA
Li
Ling-Ling
LL
Chen
Heng
H
Long
Yong-Gang
YG
Yao
D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007918:Leprosy / Q000235:genetics*
D017931:DNA Primers; D004272:DNA, Mitochondrial