Identification of sequence polymorphisms in the displacement loop region of mitochondrial DNA as a risk factor for renal cell carcinoma

Zhang, Junxia; Guo, Zhanjun; Bai, Yaling; Cui, Liwen; Zhang, Shenglei; Xu, Jinyi

doi:10.3892/br.2013.113

Cited by 16 publications

(5 citation statements)

References 26 publications

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“…We found that SNPs accumulated excessively in patients with PM/DM, although there is no evidence to support that this difference would lead to a biological effect. We reviewed previous studies on gastric cancer 23 , hepatocellular carcinoma 27 , lung cancer 28 , renal cell carcinoma 29 , lymphoma 30 , rheumatoid arthritis 12 , and systemic lupus erythematosus 13 and found that SNP accumulation was reported in hepatocellular carcinoma 27 and SLE 13 , but there were no reports of decreased SNPs in these diseases. Further studies need to be designed to characterize the role of SNP accumulation in disease progression as well as to determine whether SNP amounts positively correlated with mtDNA number is accidental or pathogenic.…”

Section: Discussionmentioning

confidence: 99%

The SNPs of mitochondrial DNA displacement loop region and mitochondrial DNA copy number associated with risk of polymyositis and dermatomyositis

Zhao

Peng

Lai

et al. 2022

Sci Rep

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Oxidative damage-induced mitochondrial dysfunction may activate muscle catabolism and autophagy pathways to initiate muscle weakening in idiopathic inflammatory myopathies (IIMs). In this study, Single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D-loop) and mitochondrial DNA (mtDNA) copy number were assessed and their association with the risk of polymyositis and dermatomyositis (PM/DM) was evaluated. Excessive D-loop SNPs (8.779 ± 1.912 vs. 7.972 ± 1.903, p = 0.004) correlated positively with mtDNA copy number (0.602 ± 0.457 vs. 0.300 ± 0.118, p < 0.001). Compared with that of the controls, the mtDNA of PM/DM patients showed D-loop SNP accumulation. In addition, the distribution frequencies of 16304C (p = 0.047) and 16519C (p = 0.043) were significantly higher in the patients with PM/DM. Subsequent analysis showed that reactive oxygen species (ROS) generation was increased in PM/DM patients compared with that in the controls (18,477.756 ± 13,574.916 vs. 14,484.191 ± 5703.097, p = 0.012). Further analysis showed that the PM/DM risk-related allele 16304C was significantly associated with lower IL-4 levels (p = 0.021), while 16519C had a trend to be associated with higher IL-2 expression (p = 0.064). The allele 16519C was associated with a positive antinuclear antibody (ANA) status in PM/DM patients (p = 0.011). Our findings suggest that mitochondrial D-loop SNPs could be potential biomarkers for PM/DM risk and these SNPs associated with cytokine expression may be involved in the development of PM/DM. Further, mtDNA copy number-mediated mitochondrial dysfunction may precede the onset of PM/DM.

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Section: Discussionmentioning

confidence: 99%

The SNPs of mitochondrial DNA displacement loop region and mitochondrial DNA copy number associated with risk of polymyositis and dermatomyositis

Zhao

Peng

Lai

et al. 2022

Sci Rep

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“…The D-loop is highly polymorphous, and the literature reports the presence of numerous changes in this region in various cancers [ 85 , 86 ]. These changes have been reported for ovarian carcinoma [ 85 ], oesophageal cancer [ 86 ], glioma [ 78 ], renal cancer [ 87 ], hepatocellular carcinoma [ 88 ] and others. Polymorphisms in the D-loop region such as 73G/A, 146T/C, 195T/C, 324C/G, 16261C/T, and 16304T/C are associated with an increased risk of developing colon cancer [ 89 ].…”

Section: Mitochondrial Dna and Carcinogenesismentioning

confidence: 53%

“…The occurrence of single nucleotide polymorphisms within the D-loop is said to increase the risk of renal-cell carcinoma [ 87 ]. Alterations in nucleotide sequences 16,293 A > G and 262 A > G concern clear-cell renal carcinoma, while 488 T > C refers to papillary tumours and benign oncocytoma [ 87 ]. As for urinary bladder cancer, there are reports about its relationship with the D-loop C16069T polymorphism [ 97 ].…”

Section: Mitochondrial Dna and Carcinogenesismentioning

confidence: 99%

The Role of Mitochondria in Carcinogenesis

Kozakiewicz

Grzybowska‐Szatkowska

Ciesielka

et al. 2021

IJMS

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The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

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“…49 In a study examining the effect of mtSNPs located more specifically within the D-loop of the control region on risk for renal cell carcinoma, mt16319 was specifically found to be reduced in cases of clear cell renal cell carcinoma. 50 Lastly, mt16362 was found to be a risk factor associated with familial breast cancer. 51 …”

Section: Discussionmentioning

confidence: 98%

Mitochondrial Variation and the Risk of Age-Related Macular Degeneration Across Diverse Populations

et al. 2014

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Substantial progress has been made in identifying susceptibility variants for age-related macular degeneration (AMD). The majority of research to identify genetic variants associated with AMD has focused on nuclear genetic variation. While there is some evidence that mitochondrial genetic variation contributes to AMD susceptibility, to date, these studies have been limited to populations of European descent resulting in a lack of data in diverse populations. A major goal of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study is to describe the underlying genetic architecture of common, complex diseases across diverse populations. This present study sought to determine if mitochondrial genetic variation influences risk of AMD across diverse populations. We performed a genetic association study to investigate the contribution of mitochondrial DNA variation to AMD risk. We accessed samples from the National Health and Nutrition Examination Surveys, a U.S population-based, cross-sectional survey collected without regard to health status. AMD cases and controls were selected from the Third NHANES and NHANES 2007-2008 datasets which include non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. AMD cases were defined as those > 60 years of age with early/late AMD, as determined by fundus photography. Targeted genotyping was performed for 63 mitochondrial SNPs and participants were then classified into mitochondrial haplogroups. We used logistic regression assuming a dominant genetic model adjusting for age, sex, body mass index, and smoking status (ever vs. never). Regressions and meta-analyses were performed for individual SNPs and mitochondrial haplogroups J, T, and U. We identified five SNPs associated with AMD in Mexican Americans at p < 0.05, including three located in the control region (mt16111, mt16362, and mt16319), one in MT-RNR2 (mt1736), and one in MT-ND4 (mt12007). No mitochondrial variant or haplogroup was significantly associated in non-Hispanic blacks or nonHispanic whites in the final meta-analysis. This study provides further evidence that mitochondrial variation plays a role in susceptibility to AMD and contributes to the knowledge of the genetic architecture of AMD in Mexican Americans.

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Identification of sequence polymorphisms in the displacement loop region of mitochondrial DNA as a risk factor for renal cell carcinoma

Cited by 16 publications

References 26 publications

The SNPs of mitochondrial DNA displacement loop region and mitochondrial DNA copy number associated with risk of polymyositis and dermatomyositis

The SNPs of mitochondrial DNA displacement loop region and mitochondrial DNA copy number associated with risk of polymyositis and dermatomyositis

The Role of Mitochondria in Carcinogenesis

Mitochondrial Variation and the Risk of Age-Related Macular Degeneration Across Diverse Populations

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