title: Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population: A case-control study.
abstract: Leukoaraiosis (LA) is a frequent neuroimaging finding commonly observed on brain MRIs of elderly people with prevalence ranging from 50% to 100%. Multiple susceptibility genes or genetic risk factors for LA have been identified in subjects of European descent. Here, we report the first replication study on several common and novel genetic variations in the Chinese population. In this study, a total of 244 subjects (201 LA patients and 43 controls) were enrolled according to our new and strict definition for LA. Subsequently, 6 genetic variants at 5 genes, rs3744028 in TRIM65, rs1055129 in TRIM47, rs1135889 in FBF1, rs1052053 in PMF1, and rs1801133 (C677T) and rs1801131(A1298C) in MTHFR, were selected for genotyping using polymerase chain reaction (PCR)-based pyrosequencing and restriction fragment length polymorphism (RFLP) together with capillary electrophoresis (CE) and agarose gel electrophoresis. Finally, Pearson's χ and multivariate logistic regression tests were used to examine the associations between the genotypes and LA. Among these candidate polymorphisms, except for rs1052053 and rs1801131, rs1135889 (P = 0.012) showed significant associations with LA in the dominant model, and the other 3 SNPs, rs3744028 (P = 0.043), rs1055129 (P = 0.038), and rs1801133 (P = 0.027), showed significant associations with LA in the recessive model. However, these differences no longer remained significant after adjusting for age, gender, hypertension, and diabetes mellitus and applying Bonferroni correction or Sidak correction for multiple testing. These results suggest that the above-mentioned genetic variants are not associated with LA risk. In summary, the study did not replicate the susceptibility of rs3744028, rs1055129, and rs1135889 at the Chr17q25 locus for LA nor did it find any other significant results for rs1052053, rs1801133, and rs1801131 in the Chinese population. It strongly indicated the ethnic differences in the genetics of LA. However, the associations of rs3744028 (TRIM65), rs1055129 (TRIM47), rs1135889 (FBF1), and rs1801133 (MTHFR) with LA before Bonferroni correction and Sidak correction for multiple testing are worth highlighting. Thus, we believe that a genome-wide association study and candidate gene association studies are needed to reassess the previous findings and screen novel risk genes for LA in China.
authors: Translational Medicine Research Center Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation Maternity and Child Health Hospital, Xiamen, Fujian, China Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian INNOVA Cell: TDx Clinics and TRANSLA Health Group, China.
authors: Wen-Qing
authors: WQ
authors: Huang
authors: Hui-Ming
authors: HM
authors: Ye
authors: Fang-Fang
authors: FF
authors: Li
authors: Ke-Hui
authors: KH
authors: Yi
authors: Ya
authors: Y
authors: Zhang
authors: Liang-Liang
authors: LL
authors: Cai
authors: Hui-Nuan
authors: HN
authors: Lin
authors: Qing
authors: Q
authors: Lin
authors: Chi-Meng
authors: CM
authors: Tzeng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D049292:Leukoaraiosis / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C095245:FBF1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C120655:PMF1 protein, human; C435227:TRIM47 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D044767:Ubiquitin-Protein Ligases; C000589384:TRIM65 protein, human