ABSTRACT
BACKGROUND AND AIMS: Mitochondrial DNA (mtDNA) haplogroups have been associated with the development of coronary artery disease (CAD) in European populations. However, the specific mtDNA haplogroups associated with CAD have not been investigated in Chinese populations. METHODS AND RESULTS: Here, we carried out a case-control study including 1036 and 481 CAD patients and 973 and 511 geographically matched asymptomatic control subjects in southern and northern China, respectively. After adjusting for age and gender, our results indicated that mtDNA haplogroups are not associated with the occurrence of CAD and its subcategories, acute coronary syndromes and stable coronary heart disease, in both southern and northern Chinese populations. By focusing on the southern Chinese population, we further revealed that mtDNA haplogroups are not associated with CAD severity. Type 2 diabetes (T2D) and hypertension are two key driving factors for the development of CAD, nonetheless, we found that the frequencies of the 12 studied mtDNA haplogroups did not differ between patients with and without T2D or hypertension. CONCLUSION: mtDNA haplogroups are not associated with the occurrence of CAD or its subcategories in Chinese populations. Other factors such as environment and nuclear genetic background may contribute to the occurrence of CAD.
Subject(s)
Acute Coronary Syndrome/genetics , Coronary Artery Disease/genetics , DNA, Mitochondrial/genetics , Genetic Variation , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , China/epidemiology , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Diabetes Mellitus/epidemiology , Female , Genetic Predisposition to Disease , Haplotypes , Humans , Hypertension/epidemiology , Male , Middle Aged , Risk Factors , Young AdultABSTRACT
Mitochondrial DNA (mtDNA) haplogroups are associated with various types of cancer; however, the molecular mechanisms by which mtDNA haplogroups affect primary hepatocellular carcinoma (HCC) are not known. In this study, we carried out a case-control study on 388 HCC patients and 511 geographically matched asymptomatic control subjects in northern China. We found that mtDNA haplogroup N9a and its diagnostic SNP, m.16257C > A, negatively correlated with the incidence of HCC in northern China (odds ratio [OR] 0.290, 95% confidence interval [CI] 0.123-0.685, p = 0.005), particularly in patients with infection of hepatitis B/C virus (HBV/HCV) (for haplogroup N9a: OR 0.213, 95% CI 0.077-0.590, p = 0.003; for m.16257C > A: OR 0.262, 95% CI 0.107-0.643, p = 0.003). However, mtDNA haplogroup N9a is not associated with clinical characteristics of HCC including serum alpha-fetoprotein (AFP) level and tumor size. In addition, cytoplasmic hybrid (cybrid) cells with N9a haplogroup (N9a10a and N9a1) had transcriptome profiles distinct from those with non-N9a (B5, D4, and D5) haplogroups. Gene set enrichment analysis (GSEA) showed that metabolic activity varied significantly between N9a and non-N9a haplogroups. Moreover, cells with haplogroup N9a negatively correlated with cell division and multiple liver cancer pathways compared with non-N9a cells. Although it is still unclear how N9a affects the aforementioned GSEA pathways, our data suggest that mtDNA haplogroup N9a is negatively correlated with the incidence and progression of HCC in northern China.
