Zhen-Xin Zhang

Association of RFC1 A80G and MTHFR C677T polymorphisms with Alzheimer's disease

We examined polymorphisms in reduced folate carrier gene (RFC1) and methylenetetrahydrofolate reductase gene (MTHFR) for association with sporadic AD (SAD) in Chinese population. Significant associations of RFC1 A80G G allele and GG genotype with SAD (p=0.008, OR=1.312, 95%CI=1.072-1.605, and p=0.042, OR=1.383, 95%CI=1.012-1.890) were found. Further stratification of total samples by APOE epsilon4 carrier status, age/age at onset and gender revealed that RFC1 A80G G allele was an APOE epsilon4-independent risk factor for late-onset AD, and it might increase the risk of AD in females. No significant associations of MTHFR C677T allele and genotype with AD were observed in total samples, but significant associations of T allele and TT genotype with AD (p=0.031, OR=1.586, 95%CI=1.042-2.414, and p=0.028, OR=2.250, 95%CI=1.074-4.712) were identified in APOE epsilon4 carrier subgroup, suggesting that MTHFR 677 T allele and APOE epsilon4 allele may synergistically act to increase AD risk. No significant effect of RFC1 G80A and MTHFR C677T polymorphisms on plasma folate and homocysteine levels was detected.

Association between Angiotensin-Converting Enzyme Gene Polymorphism and Alzheimer’s Disease in a Chinese Population

Angiotensin-converting enzyme has shown altered activity in patients with neurological diseases. An insertion/deletion (I/D) polymorphism of the DCP1 gene encoding angiotensin-converting enzyme has been reported to be associated with the risk for Alzheimer’s disease (AD), but ambiguous results have also been presented. We conducted a case-control study in a sample composed of 192 sporadic AD patients and 195 age- and sex-matched controls from Chinese Han population in Beijing and Xi’an districts to investigate the possible effect of the polymorphism. Our data revealed no association between the DCP1 polymorphism and AD risk in the total sample. There was no significant difference in the DCP1 allele or genotype frequencies between cases and controls when stratified by gender and APOE ε4 status. However, the D allele and D/D genotype were more frequent among AD patients between 66 and 70 years compared with controls (D allele: OR = 2.8, 95% CI = 1.5–5.2, p = 0.001; D/D genotype: OR = 5.9, 95% CI = 1.7–19.9, p = 0.002). Our results provided new proof that the DCP1 D allele was a probable risk factor for late-onset AD. Its role was independent and was limited to the population at a certain age.

Association of α2-macroglobulin polymorphisms and Alzheimer disease in Mainland Han Chinese

Abstract This study used case-control method to investigate roles of two α2-macroglobulin (A2M) polymorphisms, a 5-bp insertion/deletion (A2M- I / D ) and an A→G substitution (A2M- A / G ), in the development of sporadic Alzheimer disease (AD) in Mainland Han Chinese. Our results showed a trend of lower D -carrying genotype frequency in APOE-e 4 carrying AD patients than in corresponding control subjects ( χ 2 =3.67, p =0.055). The ID / AA genotype frequency was lower in AD patients comparing with controls ( χ 2 =4.04, p =0.044). In AD patients, the G -carrying genotype frequency was significantly higher in APOE-e 4 carrier subgroup than in APOE-e 4 non-carriers ( χ 2 =7.38, OR=2.99, 95% CI: 1.33–6.71, p =0.007). These results indicated that A2M- D allele was probably a weak AD protective factor, and there was a possible interaction of APOE-e 4 and A2M- G alleles to increase AD risk in Mainland Han Chinese.

Association between cathepsin D polymorphism and Alzheimer's disease in a Chinese Han population.

Cathepsin D (CTSD) is an intracellular aspartyl protease, which is active in the endosomal/lysosomal system. CTSD may play a role in Alzheimer’s disease (AD) through cleaving the amyloid precursor protein into β-amyloid peptide and degrading tau protein into fragments. A functional polymorphism in exon 2 of the cathepsin D gene (C→T, Ala224Val) has recently been reported to increase the risk for AD in some of the Caucasian populations, with a significant overrepresentation of the T allele, but these reports have not been universally duplicated. We performed an association study between CTSD polymorphism and AD in 156 sporadic AD patients and 183 controls of Chinese Han ethnicity. Our data revealed that the distribution of CTSD genotypes and alleles was similar in patients and controls. No direct association was found between CTSD polymorphism and AD risk. There might be a weak synergistic interaction between CTSD T and APOEΕ4 allele in increasing the risk for developing AD.

Association analysis of methionine synthase gene 2756 A>G polymorphism and Alzheimer disease in a Chinese population.

Homocysteine has been identified to be associated with Alzheimer disease (AD) and methionine synthase (MS) is one of the enzymes involved in homocysteine metabolism. Confused data were reported on the association between the MS 2756 A>G polymorphism and AD. To determine if this polymorphism could affect the occurrence of AD, we investigated the association between the MS 2756 A>G polymorphism and AD risk in 353 sporadic AD patients and 346 controls in a Chinese Han population. No significant differences of allele and genotype distributions between the AD cases and the controls were observed in the total samples, neither when the samples were stratified by age/age at onset and gender. When the samples were stratified by APOE epsilon4 status, a trend of A allele and AA genotype over-representation in the AD patients in comparison with the controls was observed, but it was not statistically significant (for the alleles, A versus G OR=1.549, 95% CI 0.920-2.609, p=0.098; for the genotypes, AA versus AG+GG OR=1.485, 95% CI 0.861-2.560, p=0.153). Similar trend was observed in the APOE epsilon4 non-carrier samples of the >or=65 year subgroups and it was not statistically significant too (for the alleles, A versus G OR=1.682, 95% CI 0.901-3.140, p=0.099, for the genotypes, AA versus AG+GG OR=1.690, 95% CI 0.884-3.232, p=0.110). Our data did not reveal significant association between the MS 2756 A>G polymorphism and AD development. However, a weak effect of the A allele on developing AD could not be completely excluded.

No association of the C > T polymorphism that is located 1385 upstream from initial code of fibroblast growth factor 1 gene with Alzheimer's disease in Chinese

Several lines of evidence indicate that fibroblast growth factor 1 (FGF1) confers neuroprotection against excitotocity and contributes to the selective vulnerability of neurons in entorhinal cortex in Alzheimers disease (AD). Especially, FGF1 is related to Apolipoprotein E (ApoE) expression in reactive astrocytes. Therefore, FGF1 is a promising candidate gene for AD. Two studies reported the association of a polymorphism that is located 1385bp upstream from the initial code of FGF1 gene (FGF1 -1385 C>T) polymorphism with AD. To determine whether this polymorphism could affect AD development, we investigated the association between this polymorphism and AD risk in 372 sporadic AD patients and 349 controls in a Chinese Han population. No significant difference of allele and genotype distributions between the AD cases and the controls was observed in the total samples (for the alleles, chi(2)=0.126; p=0.722; for the genotypes, chi(2)=0.089; p=0.765), neither when the samples were stratified by ApoE epsilon4-carrying status, age/age at onset and gender. Our data suggested no association between the FGF1 -1385 C>T polymorphism and AD risk in Chinese Han population.