Association Of BIN1 Gene Polymorphism With Sporadic Alzheimer's Disease And BDNF Gene Polymorphism With Vascular Cognitive Impairment In Chong Qing Area

Background:With an aging population, the morbidity rate of senile dementia increases gradually and the impact of cognitive impairment on health of old people have become prominent increasingly.Senile dementia includes Alzheimers disease(AD), vascular dementia(VD), mixed dementia(MD)and other dementia.AD is a complex and most common neurodegenerative disease in the elderly,which have two main forms of AD:familial AD(FAD) and sporadic AD(SAD).SAD is the most frequent type of AD.AD has a strong genetic component,and studies have shown that polymorphisms locate in the regions upstream the BIN1 gene can increase SAD risk.Now a novel insertion or deletion of "GGG"bases polymorphisms(rs59335482) which locates in the 28kb upstream of BIN1 gene can increase BIN1 transcriptional activity and expression levels and SAD risk.Meanwhile VD?MD and VCIND(vascular cognitive impairment no dementia)are called VCI(vascular cognitive impairment),which is a cognitive and functional impairment related to cerebrovascular disease.BDNF(brain-derived neurotrophic factor) is a member of the nerve growth factor family,which relates closely to cognitive process like learning and mermory. BDNF gene has many gene polymorphisms,which may influence gene expression and biological activity of BDNF,then lead to cognitive impairment. The software SHEsis was used to analyze the linkage disequilibrium and the haplotypes between the two groups.Objective:To investigate the association of insertion or deletion of "GGC"bases polymorphisms(rs59335482) upstream the BIN1 gene with SAD and BDNF polymorphisms with VCI in Chongqing Han population.Methods: Totally 88 patients with SAD(SAD group) and 68 health people(normal control group) were chosen simultaneously.Their genomic DNA were amplified by polymerase chain reaction(PCR) and analyzed by direct sequenced. Totally 60 patients with VCI (VCI group) 99 health (normal control group) were chosen simultaneously. The genotypes and alleles frequencies of BDNF gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results:3 genotypes(DD,ID,II) of rs59335482 were detected.rs5933 5482 genotypes frequencies between SAD group (DD(35.2%)? ID(46. 6%)?11(18.2%)) and normal control group (DD(33.8%)?ID(57.4%)?I I(8.8%)) showed no significant differences(x2=3.27, P=0.195) and allele s frequencies between SAD group (D(58.5%)?1(41.5%)) and normal c ontrol group (D(62.5%)?1(37.5%)) also showed no significant differenc es (?2=0.507, P=0.477).G11757C genotypes frequencies between VCI group (GG (30. 4%). GC (53.6%). CC (16.1%)) and normal control group (GG (3 0.9%) ?GC (47.4%). CC (21.6%)) showed no significant differences and alleles frequencies between VCI group (G (57.1%). C (42.9%)) and normal control group (G (54.6%). C (45.4%)) also showed no significant differences (?2=0.837, P=0.658; ?2=0.180, P=0.671). G196 A genotypes frequencies between VCI group(AA(23.3%).AG(51.7%). GG (25.0%)) and normal control group (AA (22.2%). AG (46.5%). GG (31.3%)) showed no significant differences and alleles frequencies between VCI group (A(49.2%). G(50.8%)) and normal control group (A(45.5%). G(54.5%)) also showed no significant differences(x2=0.7 44, P= 0.689; x2=0-413, P=0.520). BDNF C270T genotypes frequenci es (CC(8.30%). CT (56.7%). TT (35.0%) vs. CC(24.2%). CT (50. 5%). TT (25.3%)) and alleles frequency (C(36.7%). T (63.3%) vs. C(49.5%). T (50.5%)) showed significant difference between VCI gr oup and normal control group(?2=6.68, P=0.035; x2=4-98, P=0.026). And these were significant differences in the frequency haplotype G117 57C(G)-C270T(T)(Fisher's P=0.007). G196A(G)-C270T(C)(Fisher's P= 0.037). G196A(G)-C270T(T)(Fisher's P=0.031) and G11757C(G)-G196 A(G)-C270T(T)(Fisher's P=0.025) between VCI group and normal cont rol group.Conclusion:Compared to other ethnic populations,Han population of Chongqing area had its own unique rs59335482 distribution characterisrics. In Han population of Chongqing area the polymorphisms of BIN1 gene may not be related to SAD,while the polymorphisms of BDNF gene may be related to VCI.