Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome.

The mitochondrion is a crucial intracellular organelle responsible for regulating cellular energy metabolism, producing free radicals, initiating and executing the apoptotic pathways. Previous studies have shown that somatic mutations in mitochondrial DNA are associated with various tumors, which may be involved during carcinogenesis and tumor progression. To examine the mutation pattern in cancer, 625 reported somatic mutations in the mitochondrial DNA genome were analyzed. We found that, except for deletions and insertions, most somatic mutations were point mutations, accounting for 89.44% of somatic mutations. Transition was the predominant form of somatic mutation in the entire mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which were homoplastic. Frequency statistics analysis of point mutations indicated that, except for 3 tRNA genes, the mutations were distributed on all resting genes and in the D-loop region, with the latter showing the highest frequency of somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA genes showed a relatively lower frequency of somatic point mutations. Nonsynonymous mutations and terminal amino acid changes were the primary point somatic mutations detected from 13 coding-region genes, which may cause mitochondrial dysfunction in cancer cells. We found that the somatic mutations may affect the mitochondrial DNA genome; the non-coding region should be examined to identify somatic mutations as potential diagnostic biomarkers for early detection of cancer.

Genetic variations in MOV10 and CACNB2 are associated with hypertension in a Chinese Han population.

Human hypertension is a complex, multifactorial disease. Multiple variants associated with hypertension have been identified in the large numbers of genome-wide association studies, meta-analysis, and case-control studies. The present study investigated the association between the single nucleotide polymorphisms (SNPs) of five candidate genes and the susceptibility and prognosis of hypertension in a Chinese Han population. A hospital-based case-control study in a Chinese Han population was carried out, including 500 hypertension patients and 506 healthy controls. The five SNP markers were detected using the Sequenom MassArray(®) iPLEX System. The association of genotypes with susceptibility to hypertension was analyzed using odds ratio, with 95% confidence interval and logistic regression. All five variants conformed to Hardy-Weinberg proportions in the controls. No significant differences were noted in the genotype distributions for AGTR1, PRRC2A, and CALCA polymorphisms in patients with hypertension (N = 500) and healthy controls (N = 506). SNP rs2932538, a variant in MOV10, was found to be significantly associated with an increased risk of hypertension. However, SNP rs4373814, a variant in CACNB2, showed a relevant association with a decreased risk of hypertension. In conclusion, the results of our case-control study confirmed the significant association of the SNP rs2932538 in MOV10 and SNP rs4373814 in CACNB2 with an increased risk of hypertension in a Chinese Han population, suggesting that the SNP rs2932538 may be a poor prognostic indicator for hypertension, while SNP rs4373814 may be a good prognostic indicator for hypertension in the same region. However, our findings need to be replicated in larger epidemiological and functional studies.