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.

Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically?

“…Many of the above studies have undertaken the haplogroup association method which was also utilised to find an association between particular haplogroups (UKJT) and age at onset of PD [47] . Additional controversy is introduced when investigating mtDNA haplogroups and PD associations in different populations, as this can reveal very different results [48,49] . As more sophisticated techniques become available, such as mutational load analysis rather than association studies; these associations between mtDNA haplogroup and PD will become clearer and enable determination of less frequent variants.…”

Mitochondrial DNA variants as genetic risk factors for Parkinson disease

“…An A‐to‐G transition at np10398 of NADH dehydrogenase 3 of complex I mitochondrial genome, which causes an amino acid change from threonine to alanine, was suggested as a responsible variation. Separately, a series of group studies of patients of various ethnicities with Caucasian background, and patients with Asian backgrounds including Chinese and Japanese, reported inconsistent findings . Either insufficient patient numbers or population sub‐structure differences between disease and control groups were suggested as possible causes .…”

The unresolved role of mitochondrial DNA in Parkinson's disease: An overview of published studies, their limitations, and future prospects

“…al [81] and Chen et. al [82] reported no significant overall association between any of the common Asian haplogroups and PD risk.…”

“…al [72] and Chen et. al [82]) can be useful for detecting population substructure which affects the validity of results if not taken into consideration [86].…”