The Association Between Insulin-Like Growth Factor-Ⅰ Genetic Polymorphism And Alzheimer’s Disease

Background and objective:Alzheimer’s diaease (AD) is a neurodegenerative disease which common seen in eldly, its clinlical features are progressively deteriorated memory and cognition. The main pathological features of AD are the presence of intracellular neurofibrillary tangles which composed of abnormal hyperphosphory of tau protein, and extracellular senile plaque deposition, whose major constituent is amyloid (3(Aβ), accompany with massive neuronal and synapsis loss. The exact etiology of AD is complex, maybe involving both environmental and genetic risk factors. To date, a lot of researchers have established associations between the insulin-like growth factor-I (IGF-I) and Alzheimer’s disease, it plays a central role in the main pathogenesis of AD, including protects against Aβ toxicity and the rate of tau phosphorylation in neurons, by inhibiting the tau kinase glycogen synthase kinase-3(GSK-3), mean time, IGF-I influences other AD traits, such as reduce the release of endogenous acetylcholine in the hippocamp and cerebral cortex. Latese overseas researches have shown that a role of IGF-I variability in the genetic susceptibility to AD, but none relevant researches reported in China yet. The dissertation aims to analyze the relationship between the IGF-I single nucleotide polymorphisms and susceptibility to AD in China’s Hunan Han population, further explore physiological role IGF-I in the pathogenesis of AD, and provide a molecular genetic basis for the diagnosis and treatment of AD.Methods:We perfomed the case-control genetic association study, using polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) to analyze the distribution and interaction of rs35767and rs972936of IGF-I genotype, allele and haplotype in China’s Hunan Han population comprising of170AD patients and147healthy controls.Results:1. The frequencies of CC, CT, TT genotypes of IGF-I in rs35767locus were35.3%,52.4%,12.4%respectively in patients with AD, and41.5%,40.1%,18.4%respectively in control subjects. None significantly difference in the distribution of genotypes between the AD group and the controls (P>0.05). The frequencies of C, T allele were61.5%,38.5%respectively in patients with AD, and61.6%,38.4%respectively in control subjects. None significantly difference in the distribution of allele analysis between the AD group and the controls too (P>0.05).2. The frequencies of GG, AG, AA genotype of IGF-I in rs972936locus were48.8%,38.2%,12.9%respectively in patients with AD, and20.4%,40.8%,38.8%respectively in control subjects. Significantly difference exists in these two groups (x2=39.102, P=0.000<0.05), GG genotype is higher in patients with AD than in the control subjects (P<0.05). The frequencies of G, A allele were67.9%,32.1%respectively in patients with AD, and40.8%,59.2%respectively in control subjects. Significantly difference exists in these two groups (x2=46.491, P=0.000<0.05), G allele is higher in patients with AD than in the control subjects (P<0.05). These results suggesting that those carrying GG genotype or G allele may have a higher risk of AD.3. Linkage disequilibrium and haplotype analysis of rs35767and rs972936of IGF-I:The linkage disequilibrium of the two loci’s value is0.642(D’=0.642) showing in SHEsis software. Using the Haplo View software to analysis haplotype showing that:C-G and T-G haplotypes are significantly difference between AD group and controls (ORC-G=2.080, ORT-G=2.259, P<0.05), suggesting those who carrying one of these two haplotypes may bear a higher risk of AD; C-A and T-A haplotypes are also significantly difference between AD group and controls (ORc.A=0.342, ORT-A=0.583, P<0.05), suggesting those who carrying one of these two haplotypes may have a lower risk of AD.Conclusions:1. There is no obvious association between the rs35767of IGF-I polymorphism and AD attaking in Hunan Han population of China.2. GG genotype or G allele in the rs972936of IGF-I may be associated with Hunan Han population of China in the pathogenesis of AD.3. The haplotype C-G or T-G in rs35767-rs972936loci of IGF-I may positively correlated with AD, the haplotype C-A or T-A may negatively correlated with AD.