Lack of Association Between DNMT3B Polymorphisms and Sporadic Parkinson’s Disease in a Han Chinese Population

Pan, Hong; Shen, Jun; Du, Juanjuan; Cui, Shishuang; Jin, Ling; Lin, Yi‐Qi; He, Yanfang; Fu, Yang; Gao, Chao; Li, Gen; Chen, Shengdi; Ma, Jianfang

doi:10.1007/s12264-018-0233-7

Cited by 5 publications

(3 citation statements)

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“…For example, increasing evidence suggests that the DNMT3B -149C>T polymorphism, either alone or in haplotype combination with other non-coding DNMT3B polymorphisms, contributes to the maternal risk for having a child with Down syndrome [47,48,49], and has been associated with an increased risk of prematurity [30], with childhood immune thrombocytopenia [50,51] and autoimmune thyroid disease [52]. The association of the DNMT3B -149C>T polymorphism with neurological and neurodegenerative diseases, either alone or in haplotype combination, is still controversial [53,54,55,56].…”

Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels

Coppedè

Stoccoro

Tannorella

et al. 2019

IJMS

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Methylenetetrahydrofolate reductase (MTHFR) is a pivotal enzyme in the one-carbon metabolism, a metabolic pathway required for DNA synthesis and methylation reactions. MTHFR hypermethylation, resulting in reduced gene expression, can contribute to several human disorders, but little is still known about the factors that regulate MTHFR methylation levels. We performed the present study to investigate if common polymorphisms in one-carbon metabolism genes contribute to MTHFR methylation levels. MTHFR methylation was assessed in peripheral blood DNA samples from 206 healthy subjects with methylation-sensitive high-resolution melting (MS-HRM); genotyping was performed for MTHFR 677C>T (rs1801133) and 1298A>C (rs1801131), MTRR 66A>G (rs1801394), MTR 2756A>G (rs1805087), SLC19A1 (RFC1) 80G>A (rs1051266), TYMS 28-bp tandem repeats (rs34743033) and 1494 6-bp ins/del (rs34489327), DNMT3A -448A>G (rs1550117), and DNMT3B -149C>T (rs2424913) polymorphisms. We observed a statistically significant effect of the DNMT3B -149C>T polymorphism on mean MTHFR methylation levels, and particularly CT and TT carriers showed increased methylation levels than CC carriers. The present study revealed an association between a functional polymorphism of DNMT3B and MTHFR methylation levels that could be of relevance in those disorders, such as inborn defects, metabolic disorders and cancer, that have been linked to impaired DNA methylation.

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Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels

Coppedè

Stoccoro

Tannorella

et al. 2019

IJMS

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“…These results are in line with the current findings. Interestingly, there are multiple such kind studies for DNMT3B , although the results appear to be mixed ( Chen et al, 2017 ; Pezzi et al, 2017 ; Pan et al, 2018 ). The significant association of rs9305012 with PD risk is suggested in both additive and dominant models, suggesting a dominant role of the disease-susceptible T allele.…”

Section: Discussionmentioning

confidence: 99%

Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease

et al. 2023

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Background: DNA methylation plays an important role in Parkinson’s disease (PD) pathogenesis. DNA methyltransferase 1 (DNMT1) is critical for maintaining DNA methylation in mammals. The link between DNMT1 polymorphisms and PD remains elusive.Methods: The DNMT1 gene contained a total of 28 single nucleotide polymorphisms (SNPs). Four representing tag-SNPs (rs16999593, rs2162560, rs11880553, and rs9305012) were identified and genotyped in a Han Chinese population comprising 712 PD patients and 696 controls. Association analyses were performed at gene-wide significance (p < 1.8 × 10−3).Results: Rs9305012, but not the other 3 tag-SNPs, was gene-wide significantly associated with PD risk (p = 0.8 × 10−3). The rs9305012/C was a protective allele against PD (p = 1.5 × 10−3, OR 0.786, 95% CI 0.677–0.912). No significant association was observed in individual genders or PD subtypes. Haplotypes of the 4 tag-SNPs showed a significant overall distribution difference between PD patients and controls (p < 1 × 10−4). The 3-allele ACC module in the order of rs2162560, rs11880553, and rs9305012 was the highest-risk haplotype associated with PD (p < 1 × 10−4, OR 2.439, 95% CI 1.563–3.704). Rs9305012 displayed certain probability to affect transcription factor binding and target gene expression based on functional annotation analyses.Conclusion: The DNMT1 variant rs9305012 together with its haplotypes may gene-wide significantly modulate PD susceptibility. Our results support a role of DNMT1 in PD pathogenesis and provide novel insights into the genetic connection in between.

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“…MPHOSPH10 is a M-Phase Phosphoprotein involved in rRNA processing in the nucleus and cytosol. Several GWASs for neuropsychiatric diseases have identified several SNPs on MPHOSPH10 [ 54 , 55 ]. But the role of MPHOSPH10 in HCC has not been experimentally confirmed and requires further exploration.…”

Section: Discussionmentioning

confidence: 99%

A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia

Zhang,

et al. 2023

Gastroenterology Report

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Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is prevalent in East Asia. Although genome-wide association studies (GWASs) of HCC have identified 23 risk regions, the susceptibility genes underlying these associations largely remain unclear. To identify novel candidate genes for HCC, we conducted liver single-tissue and cross-tissue transcriptome-wide association studies (TWASs) in two populations of East Asia. Methods GWAS summary statistics of 2,514 subjects (1,161 HCC cases and 1,353 controls) from the Chinese Qidong cohort and 161,323 subjects (2,122 HCC cases and 159,201 controls) from the BioBank Japan project were used to conduct TWAS analysis. The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC. TWAS identified genes were further annotated by Metascape, UALCAN, GEPIA2, and DepMap. Results We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction. Of these, 13 genes were located in novel regions. Besides, we found 83 genes overlapped in the Chinese and Japanese cohorts with P < 0.05, of which, three genes (NUAK2, HLA-DQA1, and ATP6V1G2) were discerned by both single-tissue and cross-tissue TWAS approaches. Among the genes identified through TWAS, a significant proportion of them exhibit a credible role in HCC biology, such as FAM96B, HSPA5, POLRMT, MPHOSPH10, and RABL2A. HLA-DQA1, NUAK2, and HSPA5 associated with the process of carcinogenesis in HCC as previously reported. Conclusions Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.

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Lack of Association Between DNMT3B Polymorphisms and Sporadic Parkinson’s Disease in a Han Chinese Population

Abstract: Recently, several single nucleotide polymorphisms (SNPs; rs34094401 on RAD51B, rs41309351 on CPXM1, rs143555311 on MPHOSPH10, rs141620200 on SER-PINA1, and rs2424913 on DNMT3B) have been associated with Parkinson's disease (PD) in Caucasians [1-3]. Con

Cited by 5 publications

References 9 publications

Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels

Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels

Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease

A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia

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