Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts

Abstract

Drug addiction is one of the most serious social problems in the world today and addicts are always at a high risk of acquiring HIV infection. Mitochondrial impairment has been reported in both drug addicts and in HIV patients undergoing treatment. In this study, we aimed to investigate whether mitochondrial DNA (mtDNA) haplogroup could affect the risk of drug addiction and HIV-1 infection in Chinese. We analyzed mtDNA sequence variations of 577 Chinese intravenous drug addicts (289 with HIV-1 infection and 288 without) and compared with 2 control populations (n = 362 and n = 850). We quantified the viral load in HIV-1-infected patients with and without haplogroup A status and investigated the potential effect of haplogroup A defining variants m.4824A > G and m.8794C > T on the cellular reactive oxygen species (ROS) levels by using an allotopic expression assay. mtDNA haplogroup A had a protective effect against drug addiction but appeared to confer an increased risk of HIV infection in addicts. HIV-1-infected addicts with haplogroup A had a trend for a higher viral load, although the mean viral load was similar between carriers of haplogroup A and those with other haplogroup. Hela cells overexpressing allele m.8794 T showed significantly decreased ROS levels as compared to cells with the allele m.8794C (P = 0.03). Our results suggested that mtDNA haplogroup A might protect against drug addiction but increase the risk of HIV-1 infection. The contradictory role of haplogroup A might be caused by an alteration in mitochondrial function due to a particular mtDNA ancestral variant.

Mitogenome germline mutations and colorectal cancer risk in Polish population

“…In this respect it is worth noting that the mtDNA haplotypes from this study were determined for normal colon cells for patients. Moreover, in line with the international recommendations [28][29][30][31][32][33][34], the accuracy of all mitogenome sequences used here was confirmed with phylogenetic methods in previous reports [22][23][24][25][26]. The above -mentioned quality measures guarantee the authenticity of the genotyping and further association results presented in this study.…”

“…On the other hand, frequencies of non-R haplogroups were low and the frequency difference of the R macrohaplogroup between cases and controls was not large enough to consider a strong association according to the international recommendations [28][29][30][31][32][33][34]. Furthermore, this potential association was lost after Bonferroni correction.…”

“…To provide a more comprehensive insight into the relationship between mtDNA variation and colorectal cancer occurrence, the entire mitochondrial genome sequences were analysed in this study. According to the guidelines recommended by internationally recognized experts, the studies of the mtDNA associations with cancer should fulfil several requirements [28][29][30][31][32][33][34]. First and foremost, to avoid the problem of population stratification, there is a need for recruiting individuals of the same ethnic/biogeographical origin to both case and control groups.…”

“…The underpowered results suggest that the association of the R haplogroup (and its diagnostic m.12705C>T and m.16223C>T transitions) with colorectal cancer risk in the Polish population can also be explained by chance. Thus, following international recommendations [28][29][30][31][32][33][34], further validation studies replicated in larger cohorts are necessary to finally resolve the issue of the obtained associations. In fact, subsequent calculations have shown that to achieve 80% power for the two categories (R and non-R clades) the case and control groups should consist of at least 689 individuals each, whereas assuming twelve categories (haplogroups), the sample size should consist of at least 1336 individuals [27].…”

Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease, while haplogroup A mitigates the effects of PNPLA3

“…40 One study has showed that in Han Chinese patients showed that haplogroup A may decrease the risk of drug addiction. 50 This study also showed that HeLa cells overexpressing 8794T had decreased levels of ROS production compared with those overexpressing 8794C. 50 Sex has an important impact on metabolism, and sex hormones affect mitochondrial metabolism.…”