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篇目详细内容 |
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【篇名】 |
NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients |
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【刊名】 |
Frontiers of Medicine in China |
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【刊名缩写】 |
Front. Med. China |
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【ISSN】 |
1673-7342 |
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【EISSN】 |
1673-7458 |
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【DOI】 |
10.1007/s11684-010-0038-1 |
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【出版社】 |
Higher Education Press and Springer-Verlag Berlin
Heidelberg |
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【出版年】 |
2010 |
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【卷期】 |
4
卷2期 |
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【页码】 |
177-184
页,共
8
页 |
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【作者】 |
Ya-Song WU MD, PhD;
Xin-Yue CHEN MD;
Ying SHI PhD;
Hao WU MD;
De-Xi CHEN MD, PhD;
Yu SUN MD;
Fu-Jie ZHANG MD;
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【关键词】 |
nucleoside reverse transcriptase inhibitors; human immunodeficiency virus; mitochondrial DNA; D loop; mutation |
【摘要】 |
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Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, five individuals showed 73€A→G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV 2, which might contribute to the development of LD. |
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