PINK1 IVS5-5 G>A polymorphism may contribute to the risk of late onset Parkinson disease in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the possible association of IVS5-5G>A polymorphism, positioned in the upstream region of exon 5 of PINK1 gene with the risk for sporadic late onset Parkinson disease (LOPD) in Chinese.</p><p><b>METHODS</b>Intronic regulatory sequence analysis was performed using the web-based in-silico analysis. The authors performed an association study using a case-control series (comprising 382 LOPD patients and 336 controls, Chinese of Han ancestry). Genotyping was performed by PCR-based denaturing high performance liquid chromatography (DHPLC) combined with sequencing analyses. Allele and genotype frequencies were compared by the Chi-square test.</p><p><b>RESULTS</b>In-silico analysis showed that the intronic IVS5-5G>A polymorphism was located within acceptor site of exon 5 and may be the functional single polymorphism (SNP) in the regulatory region with impact on the splicing of PINK1 gene. Those result yielded statistical significant evidence for the association of PINK1 IVS5-5G>A polymorphism with risk for typical PD in Chinese Han population (OR=1.95, 95%CI: 1.29-2.94, P=0.0012). Homozygote of A allele may have increased risk for LOPD (OR=2.45, 95%CI: 1.27-4.72, P=0.009).</p><p><b>CONCLUSION</b>The authors provide the first evidence that the common genetic variation PINK1 IVS5-5G>A may contribute to the risk of LOPD in Chinese population.</p>

Polymorphisms of neural nicotinic cholinergic receptor alpha 4 gene of Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for polymorphisms in alpha 4 subunit (principal subunit of nAChR) gene (CHRNA4).</p><p><b>METHODS</b>DNA was extracted from leukocytes of all subjects including 100 healthy senior people and 100 patients with Parkinson's disease (PD). The exons and adjacent intron regions of CHRNA4 were amplified with PCR. SNPs were screened by denatured high performance liquid chromatography (DHPLC) techniques and restriction fragment length polymorphisms. Potential mutations were confirmed by sequencing.</p><p><b>RESULTS</b>Total 10 polymorphisms were detected and identified in coding and adjacent intron regions of nAChR alpha 4 gene, that are 420C/T (0.873/0.127), 870C/T (0.828/0.172), 1440A/C (0.858/0.142), 1860C/T (0.738/0.262), 1890C/T (0.605/0.395), intron 5 +14T/C (0.553/0.447), intron 2 +22G/A (0.873/0.127), intron 3 +182 Del22bp (0.813/0.187), 1758C/T and 1809C/T (reference for coding sequence is GenBank SNPs 000744), of which the last three are novel mutations. PD patients appeared higher frequency of deletion in intron 3+182(0.235) than normal controls (0.140)(P=0.015).</p><p><b>CONCLUSION</b>nAChR alpha 4 gene is polymorphic. PD patients take higher frequency of intron3+182 Del 22 bp.</p>

NQ01 gene polymorphism C609T associated with an increased risk for cognitive dysfunction and sporadic Alzheimer's disease in Chinese / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association between the C609T polymorphism of NADP (H): quinoneoxidoreductase 1 (NQ01) gene and decreased cognitive function and sporadic Alzheimer's disease (AD) in a community cohort.</p><p><b>METHODS</b>Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) and sequencing were used to determine the genotype of NQ01 in 110 subjects without cognitive dysfunction, 21 with cognitive dysfunction, and 65 AD patients from a community cohort.</p><p><b>RESULTS</b>Significantly different distributions of C/T and T/T genotypes were found between MMSE normal and abnormal subjects (OR=2.8, 95%CI 0.96-8.18, P=0.024), and between AD patients and healthy controls (OR=3.27, 95% CI 1.54-6.94, P=0.001), respectively. The frequencies of T allele of NQ01 C609T were significantly higher in MMSE abnormal subjects and AD patients (P=0.034 and 0.005) as compared to normal controls.</p><p><b>CONCLUSION</b>The C609T polymorphism of NQ01 gene may be a genetic risk factor for cognitive dysfunction and sporadic AD in Chinese population.</p>

A Chinese genetic prion disease:clinical,pathological manifestation and prion protein gene mutation analysis / 中华神经科杂志

Objective To report a large family with an autosomal dominant dementia associated with mutation in the prion protein gene(PRNP)and the detailed clinical,neuroimaging and pathological manifestations.Methods Two patients from a large family of dementia were admitted to our ward and the data of their medical history,physical examination,video electroenceplialogram,neuroimaging were colleted.A sterotactic biopsy of the right frontal lobe of the proband was done.After the informed consent from the family members obtained,the genomic DNA was extracted from peripheral blood leucocytes of 5 persons followed by in,vitro amplification using polymerase chain reaction(PCR).The PCR products were directly sequenced by Sanger method.PRNP gene sequence was also examined in 150 normal Chinese to exclude single nueleotide polymorphism.Results A missense mutation of PRNP gene in 5 farnily members was detected,resulting in Gll4V mutation in the prion protein,with M/M genotype of eodon 129.This mutation was not detected in 150 normal Chinese.The proband was diagnosed as inherited prion disease by her clinical features,including neuropsychiatrie disturbances and progressive dementia,and manifestations of neuroimaging,EEG,neuropathology and PRNP gene mutation.Conclusion The first autosomal dominant pedigree of family prion disease is found in China with G114V mutation in PRNP gene which may lead to the prion disease directly.

New polymorphism (IVS3-20 T-->C) of the parkin gene associated with the early-onset Parkinson's disease in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between a new polymorphism (IVS3-20 T>C GenBank accession number: AY463003) in intro 3 of the parkin gene and the risk for Parkinson's disease (PD) in Chinese, particularly the relation between this polymorphism and the age of onset of PD patients.</p><p><b>METHODS</b>PD was diagnosed according to the criteria of Core Assessment Program for Intracerebral Transplantations(CAPIT). All patients and controls were examined by two neurologists and were of the Han ethnic background. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC) and sequencing were used to determine the genotype of each subject.</p><p><b>RESULTS</b>A total of 312 PD patients (including 99 early-onset PD patients and 213 late-onset PD patients) and 236 controls were studied. The C/C homozygote was not found in this study. Chi-square analysis revealed that the frequencies of the C allele and T/C genotype were higher in total PD group but were not statistically different from those of the control group (P=0.6350 and 0.6331, respectively). After being stratified by age of onset, the frequency of T/C genotype was significantly higher (OR=3.52, 95%CI 0.97-13.13) in PD group with an onset age at or below 45 years old (7.07%), compared with that in the control group (2.12%). Similarly, C allele was much higher (OR=3.42, 95%CI 0.96-12.57, P=0.0276) in the early-onset PD group (3.90%) than that in the control group (1.06%). The linear trend analysis showed that both the T/C genotype and C allele increased significantly in the PD group with the increase of the onset age [chi-square(trend of Genotypes)=4.414, P=0.036; chi-square(trend of Alleles)=4.344, P=0.037]. On the other hand, there was no difference in the frequencies of allele and genotype between the late-onset PD patients and controls.</p><p><b>CONCLUSION</b>The above results suggest that the parkin IVS3-20 T>C polymorphism might be a genetic risk factor for early-onset PD in Chinese.</p>

Relationship between the Fnu4HI site polymorphism of monoamine oxidase A gene and Parkinson's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the association between the polymorphism of human monoamine oxidase type A (MAO-A) gene and Parkinson's disease(PD).</p><p><b>METHODS</b>Fnu4HI restriction fragment length polymorphism(RFLP) and PCR-RFLP were used to detect the mutation of MAO-A gene. The frequencies of alleles and genotypes at the MAO-A Fnu4HI locus on the X chromosome in different PD group were compared with those of the control group.</p><p><b>RESULTS</b>It was found that the frequencies of G allele in the patients with PD and controls were 0.613 and 0.527 respectively, P=0.039 "the frequencies of TT genotype were 0.303 and 0.415(P=0.014), and the frequencies of GG genotype were 0.564 and 0.451 respectively(P=0.021). When the patients were divided into two groups by age-onset, significant difference in the allelic and genotypic frequencies was observed only between early-onset PD group and control group. And when the PD patients were grouped by sex, significant difference was observed only between male PD group and male control group (the frequencies of G allele being 0.669 and 0.500 respectively, P=0.005).</p><p><b>CONCLUSION</b>This study revealed significant differences between PD group and control group in allelic and genotypic frequencies. The findings supported the hypothesis about an association between MAO-A gene and PD, suggesting that age at onset of PD and gender predisposition might be related to the putative association, and Fnu4HI SNP be a risk factor for PD.</p>

Change of ?-amyloid precursor protein processing in platelet of Alzheimer's disease patients / 中华神经科杂志

Objective To investigate the characteristic of ?-amyloid precursor protein (A?) processing in activated platelet in AD.Methods Thirty-six sporadic AD patients and 30 control subjects were included in this study.Blood was collected from the subjects to separate platelets.After treated by thrombin,the soluble amyloid precursor protein (APP) level in the snpernatants of platelets from 36 were analyzed by means of western blot with a specific antibody recognizing soluble APP.Meanwhile A? level was measured by radioimmunoassay.Results After treated with thrombin,the level of soluble APP in the supernatants of platelets in patients with AD decreased by 31.0% (P