Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

Abstract

Background: Mitochondrial dysfunction is linked to the pathogenesis of Parkinson's disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.

Methods: Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.

Results: Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082-0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030-0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112-11.523, P = 0.033), other haplogroups also did not show significant differences in the group.

Conclusions: Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.

Figure 1

Classification of major Asian mitochondrial DNA haplogoups.

Figure 2

Polymerase chain reaction-restriction fragment length polymorphism products of mitochondrial DNA single nucleotide polymorphism A10398G and C10400T analyzed with agarose gel electrophoresis. Lane M: D2000 marker; Lane 1: 10398G and 10400T; Lane 2: 10398A and10400C.

Figure 3

Polymerase chain reaction-restriction fragment length polymorphism analysis of mitochondrial DNA single nucleotide polymorphism A663G, C5178A, A13263G, A4833G, C12705T, T6392C, and 8280–8290 = A[delCCCCCTCTA] G. (a) Lane M: D2000 marker; Lane 1: 663G; Lane 2: 663A; Lane 3: 5178A; Lane 4: 5178C; Lane 5: 13263G; Lane 6: 13263A; Lane 7: 4833G; Lane 8: 4833A; (b) Lane M: D2000 marker; Lane 1: 12705C; Lane 2: 12705T; (c) Lane M: D2000 marker; Lane 1: 6392C; Lane 2: 6392T; (d) Lane M: Marker-20-bp Ladder; Lane 1: 9-bp Del (+); Lane 2: 9-bp Del (−).

Figure 4

Direct sequencing of the mitochondrial DNA fragments to confirm the alleles of each single nucleotide polymorphism. *Forward sequencing for all of the polymerase chain reaction-amplified fragments except the one encompassing C12705T which was detected by reverse sequencing.