Single Nucleotide Polymorphisms In D-loop Research Articles

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

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.

Polymorphisms and haplotype of mitochondrial DNA D-loop region are associated with polycystic ovary syndrome in a Chinese population

Polymorphisms in mitochondrial DNA (mtDNA) have been linked to a range of diseases. Here we investigate the relationship between mtDNA D-loop region polymorphisms, mtDNA haplotype and polycystic ovary syndrome (PCOS), as well as the correlation of D-loop variants and clinical characteristics of PCOS, in a Chinese population. The mtDNA D-loop of whole blood samples from 421 PCOS patients and 409 controls underwent next generation sequencing. The variants G207A (PBH＜0.05), 16036GGins (PBH＜0.05) and 16049Gins (PBH＜0.001) were associated with decreased risk of PCOS. No variants were associated with PCOS, and within the PCOS group, no statistical significance was found between D-loop polymorphisms and clinical characteristics. Patient haplotype was identified from D-loop single nucleotide polymorphisms and analysis suggested that haplotype A15 (P adjusted ＜0.01) was significantly associated with decreased risk of PCOS. In conclusion, mtDNA D-loop alterations and haplotype appear to confer resistance to PCOS in Chinese women.

Association between mitochondrial DNA D-loop region polymorphisms and endometriosis in a Chinese population.

To investigate the correlation between endometriosis and mitochondrial DNA (mtDNA) D-loop single nucleotide polymorphisms (SNPs) and haplotype, as well as the predictive power of certain SNPs in reproductive outcomes in a Chinese Han population. A case-control study was conducted in which 125 endometriosis patients and 124 controls were recruited from an academic fertility center. The entire 1124-bp D-loop region of mtDNA of whole blood samples from all subjects was amplified, sequenced, and compared with the revised Cambridge Reference Sequence (rCRS) to identify SNPs and haplotypes. The association between D-loop SNPs and embryo quality and clinical outcome following in vitro fertilization (IVF) was also assessed. A total of 321 polymorphisms were identified by sequencing, allowing comparison of the D-loop between endometriosis patients and controls. The frequency of the AC523-524 del, T16172C, and C16290T variants were significantly higher, while the frequency of polymorphisms T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins were lower, in the endometriosis group compared with the control group (p < 0.05). Within the endometriosis group, the high-quality blastocyst rate in the 16,290T subgroup was significantly lower than that in the 16290C subgroup (p < 0.05). In the control group, 16519C carriers showed a lower rate of high-quality blastocyst development compared with 16519T (p < 0.05). In endometriosis patients clinical pregnancy rate was significantly lower in the 150T subgroup compared with the 150C subgroup (p < 0.05). Data confirms a correlation between D-loop polymorphisms and endometriosis. The polymorphisms AC523-524 del, T16172C, and C16290T are associated with increased risk of endometriosis, while T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins are associated with decreased risk of endometriosis. In addition, C16290T and T16519C can be associated with poor quality blastocyst development in population with and without endometriosis, respectively and C150T can be a predictor of poor IVF outcome.

Cancer risk associated single nucleotide polymorphisms of mitochondrial D-loop and 8-hydroxy-2'-deoxyguanosine levels in gastric cancer

ABSTRACTThe accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) is related to gastric carcinogenesis. To evaluate the potential relationships between DNA damage and D-loop SNPs, we measured the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the gastric cancer tissue by immmunostaining. Our data showed that the gastric cancer susceptibility SNP of 16519C was associated with higher 8-OHdG levels. Taken together, the cancer-risk associated D-loop SNPs might initiate carcinogenesis through increasing oxidative damage.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with colorectal cancer outcome

Single nucleotide polymorphisms (SNPs) in the displacement loop (D-Loop) of mitochondrial DNA (mtDNA) has been identified for their association with the risk and outcome in many cancers. We have identified risk associated D-loop SNPs for colorectal cancer previously, in the present study, we evaluate their prognostic value for postoperative survival of colorectal cancer (CRC). The minor haplotype of nucleotides 16290T and frequent haplotype of nucleotide 16298T in the hypervariable segment 1 (HV1) region of the D-loop were identified for their association with high survival rate of CRC. After adjusted with COX proportional hazard model, the nucleotide site of 16290 was identified as independent predictor for CRC (RR, 0.379; 95% CI, 0.171–0.839; p = 0.017). In conclusion, SNPs in the mtDNA D-Loop were found to be valuable markers for colorectal cancer outcome evaluation.

Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as risk biomarker for liposarcoma

Single nucleotide polymorphisms (SNPs) in the Displacement-loop (D-loop) region of mitochondrial DNA have been reported to be associated with cancer risk in various types of cancer. To assess the frequency of D-loop SNPs in a large series of liposarcoma and establish correlations with cancer risk, we sequenced the D-loop of 82 liposarcoma patients and analyzed their use as predictive biomarkers for liposarcoma risk. The minor alleles of nucleotides 73G, 523–524del, 16,290T, 16,319A, 16,356C were associated with an increased risk for liposarcoma patients, whereas the insertion of C at the site 315 (located within the D310) were associated with a decreased risk for liposarcoma patients. These results suggest that SNPs in the mitochondrial D-loop should be considered as a biomarker which may be useful for the early detection of liposarcoma in individuals at risk of this cancer.

Identification of sequence polymorphisms in the D-Loop region of mitochondrial DNA as a risk factor for gastric cancer

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-Loop) of mitochondrial DNA (mtDNA) has been identified for their association with cancer risk in different types of cancers. We investigated the gastric cancer risk profile of D-Loop SNPs in a case-control study. The frequent alleles of nucleotides 73G/A, 235A/G, 309C/C insert, 324C/G, 16,362T/C and 16,519C/T were significantly associated with an increased risk for gastric cancer, whereas the frequent alleles of nucleotides 523–524AC/del were associated with resistance to gastric cancer. In conclusion, SNPs in the mtDNA D-Loop were found to be valuable markers for gastric cancer risk evaluation.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease

Background The mitochondrial displacement loop (D-loop) accumulates mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). We previously identified disease riskassociated SNPs in the D-loop of chronic kidney disease (CKD) patients; in this study, we investigated the association of age-at-onset and D-loop SNPs in CKD patients. Methods The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008. The age-at-onset curve of the CKD patients was calculated using the Kaplan-Meier method at each SNP site, and compared using the log-rank test. Results The mean age of 119 CKD patients was (55.6±14.2) years, and 56.3% were males. The mean estimated glomerular filtration rate (eGFR) was (81.2±12.4) ml·min−1·1.73 m−2, with 79.8% (n=95) of patients having an eGFR &lt;60 ml·min−1·1.73 m−2. All participants had an eGFR &gt;30 ml·min−1·1.73 m−2. The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients. The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test. The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site (P=0.010). Conclusions Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.

Single nucleotide polymorphisms in the mitochondrial displacement loop region modifies malignant melanoma: a study in Chinese Han population

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. We investigated the malignant melanoma (MM) risk profile of D-loop SNPs in a case-controlled study in Chinese Han population. A statistically significant increase in SNP frequency for the T16362C, A16399G and T195C alleles was observed in MM patients (p < 0.05) comparing the MM patients to controls, which indicted that the patients who carry these alleles were susceptible to MM. The study identified SNPs in the mitochondrial D-loop could increase MM risk in Chinese Han people. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a higher risk of developing MM in Chinese Han population, thereby helping to make therapeutic decisions for these patients.

Single nucleotide polymorphisms in the mitochondrial displacement loop region and outcome of malignant fibrous histiocytoma

Purpose: Single nucleotide polymorphisms (SNPs) in the mitochondrial DNA displacement-loop (D-loop) region have been reported to be associated with cancer risk and disease outcome in several types of cancer. In this study, we investigated whether the SNPs in mitochondrial D-loop were associated with the outcome of malignant fibrous histiocytoma (MFH). Experimental design: The D-loop region of mtDNA was sequenced for 80 MFH patients. The 3 years survival curve were calculated with the Kaplan–Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method. Results: The SNP sites of nucleotides 152T/C, 16,390G/A, 16,290C/T, 16,304T/C and the AC deletion at sites 523 and 524 were identified for prediction of post-operational survival by the log-rank test. In an overall multivariate analysis, the 16,290 and 16,390 alleles were identified as independent predictors of MFH outcome. The length of survival for patients with the rare allele 16,390A genotype was significantly shorter than that for patients with the frequent allele 16,390Gat the site 16,390. The same was seen for the rare allele 16,290T genotype when compared with matched allele 16,290C at the site 16,290 in MFH patients. Conclusions: These results suggested that SNPs in the D-loop are independent prognostic markers for patients with MFH. The analysis of genetic polymorphisms in the D-loop can help identify patient subgroups at higher risk of a poor disease outcome.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA are associated with epithelial ovarian cancer prognosis

Objective: The single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) is found in many types of cancers. A lot of reports show the SNPs of D-loop may be related to cancers prognosis. This study investigated whether the SNPs were associated with the outcome of epithelial ovarian cancer (EOC). Method: The D-loop region of mtDNA samples from blood were obtained from 89 patients with primary EOC, who received surgery. The 3 year survival curves were calculated by Kaplan–Meier method and compared by the log-rank test. Multivariate analysis was performed with Cox proportional hazards model. Result: The SNP sites of nucleotides 309 C/T, 324 C/G and 446 C/A were identified for prediction of post-operational survival. In an overall multivariate analysis, the alleles 309 and 324 were identified as independent predictors of EOC outcome. Conclusion: The results indicated that the SNPs in D-loop are associated with the clinical outcome of patients with EOC. The analysis of SNPs in D-loop region may help identify the patient genotype to predict prognosis of the EOC patients.

Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as risk biomarkers for malignant fibrous histiocytoma

Single nucleotide polymorphisms (SNPs) in the mitochondrial DNA Displacement-loop (D-loop) region particularly in a highly polymorphic homopolymeric C stretch named D310 have been reported to be associated with cancer risk in several types of cancer. In order to evaluate the frequency of D-loop SNPs in a large series of malignant fibrous histiocytoma (MFH) and establish correlations with cancer risk, we sequenced the D-loop of 92 MFH patients and analyzed their use as predictive biomarkers for MFH risk. The minor alleles of nucleotides 73G, 151T were associated with an increased risk for MFH patients, whereas the alleles of nucleotides 16,298C, 152C, and insertion of C at the site 315 (located within the D310) were associated with a decreased risk for MFH patients. These results suggest that SNPs in the mitochondrial D-loop should be considered as a biomarker which may be useful for the early detection of MFH in individuals at risk of this cancer.

Sequence polymorphisms in the D-loop region of mitochondrial DNA and outcome of non-Hodgkin lymphoma

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) might be associated with cancer risk and disease outcome. We have identified 140 SNPs including 26 SNPs with frequency distribution of minor allele greater than 5% in a case–control study for non-Hodgkin lymphoma patients previously. In this study, we assessed the predictive power of D-loop SNPs in NHL patients. Five SNP sites were identified by log-rank test for statistically significant prediction of NHL survival in a univariate analysis. In an overall multivariate analysis, allele 16304 was identified as an independent predictor of NHL outcome. The survival time of NHL patients with 16304C was significantly shorter than that of patients with 16304T (relative risk, 0.513; 95% CI, 0.266–0.989; p = 0.046). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of a poor disease outcome.

Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as a risk factor for non-Hodgkin lymphoma

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. We investigated the non-Hodgkin lymphoma (NHL) risk profile of D-loop SNPs in a case–control study. The minor alleles of nucleotides 73A/G, 263A/G, 315C/C insert were associated with a decreased risk for NHL. The minor alleles of the nucleotides 200G/A were specifically associated with the risk of diffuse large B-cell lymphoma, whereas the minor allele of nucleotides 16362C/T and 249Del/A was specifically associated with the decreased risk of T-cell lymphoma. In conclusion, SNPs in mtDNA are potential modifiers of NHL risk. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of developing NHL.