Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
Associations between a polymorphism in the pleiotropic GCKR and Age-related phenotypes: the HALCyon programme.
复制标题
DOI：
10.1371/journal.pone.0070045
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
HALCyon study team
中科院分区：
文献类型：
--
作者：
Alfred T;Ben-Shlomo Y;Cooper R;Hardy R;Deary IJ;Elliott J;Harris SE;Kivimaki M;Kumari M;Power C;Starr JM;Kuh D;Day IN;HALCyon study team
GCKR编码的葡萄糖激酶调节蛋白在葡萄糖代谢中起着重要作用，该基因的单核苷酸多态性（SNP）rs 1260326（P446 L）与几种年龄相关的生物标志物相关，包括甘油三酯、葡萄糖、胰岛素和载脂蛋白。然而，该基因中的SNPs与其他衰老表型（如认知和身体能力）之间的关联尚未报道。作为整个生命过程中的健康老龄化（HALCyon）合作研究计划的一部分，来自5个年龄在44岁至90岁以上的英国队列的男性和女性进行了rs 1260326基因分型。荟萃分析用于汇集研究内SNP与几种年龄相关表型之间的基因型关联，包括体重指数（BMI），血脂水平，肺功能以及认知和身体能力。我们证实了SNP的次要等位基因与较高的甘油三酯和较低的葡萄糖水平之间的关联。我们还观察到次要等位基因与较低BMI之间存在非依赖性的关联（合并的z评分β =-0.04，p值= 0.0001，n = 16，251）。 此外，有一些证据表明基因-环境相互作用，包括体力活动减弱对甘油三酯的影响。然而，没有观察到与认知和身体能力的测量相关。从中年到老年人的研究结果证实了rs 1260326 GCKR与甘油三酯和葡萄糖之间的关联，表明可能的基因-环境相互作用，但没有提供证据表明其相关性延伸到认知和身体能力。
The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability. We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score = −0.04, p-value = 0.0001, n = 16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability. Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.
登录
查看更多内容
影响因子：
37.8
作者：
Dehghan A;Dupuis J;Barbalic M;Bis JC;Eiriksdottir G;Lu C;Pellikka N;Wallaschofski H;Kettunen J;Henneman P;Baumert J;Strachan DP;Fuchsberger C;Vitart V;Wilson JF;Paré G;Naitza S;Rudock ME;Surakka I;de Geus EJ;Alizadeh BZ;Guralnik J;Shuldiner A;Tanaka T;Zee RY;Schnabel RB;Nambi V;Kavousi M;Ripatti S;Nauck M;Smith NL;Smith AV;Sundvall J;Scheet P;Liu Y;Ruokonen A;Rose LM;Larson MG;Hoogeveen RC;Freimer NB;Teumer A;Tracy RP;Launer LJ;Buring JE;Yamamoto JF;Folsom AR;Sijbrands EJ;Pankow J;Elliott P;Keaney JF;Sun W;Sarin AP;Fontes JD;Badola S;Astor BC;Hofman A;Pouta A;Werdan K;Greiser KH;Kuss O;Meyer zu Schwabedissen HE;Thiery J;Jamshidi Y;Nolte IM;Soranzo N;Spector TD;Völzke H;Parker AN;Aspelund T;Bates D;Young L;Tsui K;Siscovick DS;Guo X;Rotter JI;Uda M;Schlessinger D;Rudan I;Hicks AA;Penninx BW;Thorand B;Gieger C;Coresh J;Willemsen G;Harris TB;Uitterlinden AG;Järvelin MR;Rice K;Radke D;Salomaa V;Willems van Dijk K;Boerwinkle E;Vasan RS;Ferrucci L;Gibson QD;Bandinelli S;Snieder H;Boomsma DI;Xiao X;Campbell H;Hayward C;Pramstaller PP;van Duijn CM;Peltonen L;Psaty BM;Gudnason V;Ridker PM;Homuth G;Koenig W;Ballantyne CM;Witteman JC;Benjamin EJ;Perola M;Chasman DI
通讯作者：
Chasman DI
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Baltes, PB;Lindenberger, U
通讯作者：
Lindenberger, U
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3
作者：
Gallacher, John;Bayer, Anthony;Ben-Shlomo, Yoav
通讯作者：
Ben-Shlomo, Yoav