Mitochondria are responsible for energy production in unicellular and multicellular eukaryotes. Apart from their major role in metabolism, mitochondria are involved in many other cellular processes. A new paradigm is needed to understand aging, aging-related illnesses, and complex diseases. Because of the long co-evolution of mitochondria with the cells, subtle variations in the function of these organelles could influence many organ systems. Understanding the extent of this influence will shed light on the pathophysiology of some of these diseases. This review will examine the history of mitochondrial DNA research, and explain the role mitochondrial DNA plays in relation to complex diseases and their outcomes, like metabolic diseases, cancer and obesity. Finally, we will explore some of the new paradigms used in this research.

Abstract. Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies.

Glutathione S-transferases (GSTs) are a group of phase II detoxification enzymes, which catalyze the conjugation of glutathione (GSH) with carcinogens, among other xenobiotics. The GSTM3 gene is part of the GSTs gene family, and its polymorphism A/B has been associated with risk and protective effects of several cancers. This genetic variant is a deletion of 3 bp (AGG) in intron 6. Previous association studies have performed genotyping using techniques such as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In this study, we took advantage of the TaqMan(®) probes features and developed a reliable, faster, more simple and economic method to identify the 3-bp deletion. Our allelic discrimination method was able to distinguish between homozygous A/A, heterozygous A/B and homozygous B/B samples, as shown by TaqMan(®) based real-time PCR. Results were validated by Sanger Sequencing. In conclusion, we developed a specific and rapid method to detect the 3-bp deletion from the GSTM3 A/B polymorphism.

In 2015, according to the National Institute of Statistics and Geography (INEGI), malignant breast tumors were the first cause of cancer fatality in women (6,273 fatalities) in Mexico, whereas 2,793 fatalities in women were due to ovarian cancer. A total of 5–10% of breast cancer and 10–15% of ovarian cancer cases are caused by a hereditary breast-ovarian cancer syndrome, with mutations predominantly identified in the BRCA1 and BRCA2 genes. Recently, the Mexican founder mutation BRCA1 ex9-12del was identified (deletion of exons 9–12 with recombination between introns 8–12). This is the most frequently reported mutation in hereditary breast/ovarian cancer in Mexico. Current detection methods include end-point polymerase chain reaction (PCR) and Multiplex Ligation-dependent Probe Amplification (MLPA). In the present study a cheap, sensitive and fast detection method was developed based on quantitative PCR and two TaqMan® probes, one to detect the deletion (recombination region between introns 8 and 12), and the other one a region from exon 11. With this assay, 90 samples were able to be analyzed in 2 h using 2.5 ng of DNA/reaction at a cost of ~2–3 USD. This method is capable of detecting positive samples for DNA deletion and excluding negative ones. Therefore, the method proposed may be a useful high-throughput diagnostic option that could be useful in future association or prevalence studies that use large populations.