CD33 rs3865444多态性与红水河流域长寿人群血脂水平的相关性
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摘要
目的探讨广西红水河流域长寿人群CD33 rs3865444多态性与血脂水平的相关性。方法应用改良的多重高温连接酶检测反应技术(i MLDR)对该流域壮族长寿老人(长寿组,≥90岁,n=645)、非长寿老人(当地对照组,60～77岁,n=674)以及贺州非长寿家系(外地对照组,60～77岁,n=662)进行CD33 rs3865444多态性位点进行基因分型,并分析各基因型对体重指数、血压、空腹血糖及血脂指标等心血管危险因素的影响。结果红水河流域女性CD33 rs3865444等位基因A频率及基因型(CA/AA)频率明显高于外地对照组,长寿组女性CA/AA基因型频率明显高于男性,而外地对照组女性CA/AA基因型频率则明显低于男性。长寿组男性A等位基因携带者TC、LDLC及载脂蛋白B水平明显高于非A等位基因携带者(P均<0.0001);当地对照组女性A等位基因携带者HDLC低于非A等位基因携带者,而外地对照组女性A等位基因携带者HDLC及载脂蛋白A则高于非A等位基因携带者。结论 CD33 rs3865444多态性与血脂水平有一定的关系,但受性别及环境等因素的影响。A等位基因在长寿女性中富集的意义有待进一步研究。
Aim To investigate the possible relationship between variant CD33 rs3865444 and serum lipid levels in long-lived population inhabiting along Hongshuihe River Basin in Guangxi province. Methods Genotyping of CD33 rs3865444 locus was performed by improved multi-temperature ligase detection reaction technique( i MLDR) for long-lived individuals( long-lived group,aged≥90 years,n = 645),non-long-lived elderly( local control group,aged 60 ～ 77 years,n = 674) residing in Hongshuihe River Basin and non-long-lived elderly living in Hezhou( non-local control group,aged 60～ 77 years,n = 662),a town about 600 km from Guangxi Honeshuihe. Association of CD33 rs3865444 genotypes with lipids was analyzed thereafter. Results The frequencies of A allele and its genotype( CA/AA) of females in Hongshuihe River Basin,both long-lived group and long control group,were significantly higher than those of non-local controls;CA/AA genotype of females was higher than that of males in the long-lived group,while this status was opposite between gender in the non-local controls. The levels of TC,LDLC and Apo B of A allele carriers in males in long-lived group were dramatically greater than those of non-A allele carriers( P<0.0001),while HDLC level of A carriers was lower than non-A carriers in females of local controls; by contrary,HDLC and Apo A levels of females were higher than those of non-A carriers in the non-local controls. Conclusions CD33 rs3865444 polymorphism correlates with lipid levels to some extent,which is influenced by sex and other environmental factors. The enrichment of A allele of CD33 rs3865444 locus in the long-lived females needs further clarification.
Aim To investigate the possible relationship between variant CD33 rs3865444 and serum lipid levels in long-lived population inhabiting along Hongshuihe River Basin in Guangxi province. Methods Genotyping of CD33 rs3865444 locus was performed by improved multi-temperature ligase detection reaction technique( i MLDR) for long-lived individuals( long-lived group,aged≥90 years,n = 645),non-long-lived elderly( local control group,aged 60 ～ 77 years,n = 674) residing in Hongshuihe River Basin and non-long-lived elderly living in Hezhou( non-local control group,aged 60～ 77 years,n = 662),a town about 600 km from Guangxi Honeshuihe. Association of CD33 rs3865444 genotypes with lipids was analyzed thereafter. Results The frequencies of A allele and its genotype( CA/AA) of females in Hongshuihe River Basin,both long-lived group and long control group,were significantly higher than those of non-local controls;CA/AA genotype of females was higher than that of males in the long-lived group,while this status was opposite between gender in the non-local controls. The levels of TC,LDLC and Apo B of A allele carriers in males in long-lived group were dramatically greater than those of non-A allele carriers( P<0.0001),while HDLC level of A carriers was lower than non-A carriers in females of local controls; by contrary,HDLC and Apo A levels of females were higher than those of non-A carriers in the non-local controls. Conclusions CD33 rs3865444 polymorphism correlates with lipid levels to some extent,which is influenced by sex and other environmental factors. The enrichment of A allele of CD33 rs3865444 locus in the long-lived females needs further clarification.
引文
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[9]Proitsi P,Lupton MK,Velayudhan L,et al. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease:A mendelian randomization analysis[J]. PLoS Med,2014,11(9):e1001713.
[10]Jin P,Pan Y,Pan Z,et al. Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging[J]. Lipids Health Dis,2018,17(1):61.
[11]Liu Q,An Y,Ma W,et al. High cholesterol diet results in elevated amyloidβand oxysterols in rats[J]. Mol Med Rep,2018,17(1):1235-1240.
[12]Li X,Shen N,Zhang S,et al. CD33 rs3865444 polymorphism contributes to Alzheimer's disease susceptibility in Chinese,European,and North American populations[J].Mol Neurobiol,2015,52(1):414-421.
[13]Chung SJ,Lee JH,Kim SY,et al. Association of GWAS top hits with late-onset Alzheimer disease in Korean population[J]. Alzheimer Dis Assoc Disord,2013,27(3):250-257.
[14]Jing C,Hui LI,Qin ZD,et al. Y-chromosome genotyping and genetic structure of Zhuang populations[J]. Acta Genetica Sinica,2006,33(12):1060-1072.
[15]Gan RJ,Pan SL,Mustavich LF,et al. Pinghua population as an exception of Han Chinese's coherent genetic structure[J]. J Hum Genet,2008,53(4):303-313.
[2]Schwarz F,Springer SA,Altheide TK,et al. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline[J]. Proc Natl Acad Sci U S A,2016,113(1):74-79.
[3]Mao YF,Guo ZY,Pu JL,et al. Association of CD33 and MS4A cluster variants with Alzheimer's disease in East Asian Populations[J]. Neurosci Lett,2015,609:235-239.
[4] Mcmillan S,Crocker P. CD33-related sialic-acid-binding immunoglobulin-like lectins in health and disease[J]. Carbohydr Res,2008,343(12):2050-2056.
[5]Walker DG,Whetzel A,Serrano G,et al. Association of CD33 polymorphism rs3865444 with Alzheimer's disease pathology and CD33 expression in human cerebral cortex[J].Neurobiol Aging,2015,36(2):571-582.
[6]Deng YL,Liu LH,Wang Y,et al. The prevalence of CD33and MS4A6A variant in Chinese Han population with Alzheimer's disease[J]. Hum Genet,2012,131(7):1245-1249.
[7] Tan L,Yu JT,Zhang W,et al. Association of GWASlinked loci with late-onset Alzheimer's disease in a northern Han Chinese population[J]. Alzheimers Dement,2013,9(5):546-553.
[8] Lesser GT,Haroutunian V,Purohit DP,et al. Serum lipids are related to Alzheimer's pathology in nursing home residents[J]. Dement Geriatr Cogn Disord,2009,27(1):42-49.
[9]Proitsi P,Lupton MK,Velayudhan L,et al. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease:A mendelian randomization analysis[J]. PLoS Med,2014,11(9):e1001713.
[10]Jin P,Pan Y,Pan Z,et al. Alzheimer-like brain metabolic and structural features in cholesterol-fed rabbit detected by magnetic resonance imaging[J]. Lipids Health Dis,2018,17(1):61.
[11]Liu Q,An Y,Ma W,et al. High cholesterol diet results in elevated amyloidβand oxysterols in rats[J]. Mol Med Rep,2018,17(1):1235-1240.
[12]Li X,Shen N,Zhang S,et al. CD33 rs3865444 polymorphism contributes to Alzheimer's disease susceptibility in Chinese,European,and North American populations[J].Mol Neurobiol,2015,52(1):414-421.
[13]Chung SJ,Lee JH,Kim SY,et al. Association of GWAS top hits with late-onset Alzheimer disease in Korean population[J]. Alzheimer Dis Assoc Disord,2013,27(3):250-257.
[14]Jing C,Hui LI,Qin ZD,et al. Y-chromosome genotyping and genetic structure of Zhuang populations[J]. Acta Genetica Sinica,2006,33(12):1060-1072.
[15]Gan RJ,Pan SL,Mustavich LF,et al. Pinghua population as an exception of Han Chinese's coherent genetic structure[J]. J Hum Genet,2008,53(4):303-313.