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Influence of four polymorphisms in ABCA1 and PTGS2 genes on risk of Alzheimer’s disease: a meta-analysis

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Abstract

We preformed this meta-analysis to investigate the influence of ABCA1 (ATP-binding cassette sub-family A member 1) rs2422493 (C-477T), rs1800977 (C-14T), rs2066718 (V771M), and PTGS2 (Prostaglandin-endoperoxide synthase 2) rs20417 (G-765C) polymorphisms on the risk of Alzheimer’s disease (AD). Seventeen eligible case–control studies were acquired from PubMed, Embase, Alzgene, Chinese National Knowledge Infrastructure and Wanfang databases. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated to evaluate the association under five genetic models. Combined data indicated that ABCA1 rs2422493 polymorphism was statistically significant associated with increasing AD risk in three genetic models (allelic T vs C: OR = 1.12, 95 % CI: 1.01–1.24; homozygous TT vs CC: OR = 1.26, 95 % CI: 1.03–1.55; and recessive TT vs TC + CC: OR = 1.33, 95 % CI: 1.12–1.58) while no association was found between two other ABCA1 polymorphisms and AD susceptibility. Nevertheless, a further risk-stratification analysis showed that ApoE-ε4 carriers with any ABCA1 polymorphism suffered a much higher probability to be AD patients. Meanwhile, PTGS2 rs20417 polymorphism was linked to decreasing AD risk with a P < 0.0001 in five genetic models (e.g., allelic C vs G: OR = 0.59, 95 % CI: 0.50–0.70; homozygous CC vs GG: OR = 0.31, 95 % CI: 0.18–0.52; and heterozygous CG vs GG: OR = 0.64, 95 % CI: 0.52–0.78). In summary, our meta-analysis results showed that ABCA1 rs2422493 polymorphism was a risk factor for AD while PTGS2 rs20417 variant showed a protective effect on AD risk. In addition, ABCA1 rs2066718 and rs1800977 polymorphisms might not contribute to AD susceptibility in general population, but they should play a role on AD development when interacted with ApoE-ε4.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (31170676), and by the funds from Sail Plan ‘the Introduction of the Shortage of Top-Notch Talent’ Project [YueRenCaiBan (2014) 1] as well as Education Discipline Construction Project (2013KJCX0090) of Guangdong Province, China.

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    Authors and Affiliations

    1. Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, 523808, Guangdong, People’s Republic of China

      Qicong Chen, Biyu Liang, Ziyou Wang, Xiaoguang Cheng & Zunnan Huang

    2. School of Preclinical Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, People’s Republic of China

      Qicong Chen

    3. Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong, People’s Republic of China

      Biyu Liang

    4. School of Pharmacy, Guangdong Medical University, No. 1 Xincheng Road, Dongguan, 523808, Guangdong, People’s Republic of China

      Yifeng Huang, Yong Liu & Zunnan Huang

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    1. Qicong Chen
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    Chen, Q., Liang, B., Wang, Z. et al. Influence of four polymorphisms in ABCA1 and PTGS2 genes on risk of Alzheimer’s disease: a meta-analysis. Neurol Sci 37, 1209–1220 (2016). https://doi.org/10.1007/s10072-016-2579-9

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