Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals.
Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals.
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DOI：
10.2337/dc11-2006
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发表时间：
2012-08
期刊：
影响因子：
16.2
通讯作者：
Tobe K
中科院分区：
文献类型：
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作者：
Iwata M;Maeda S;Kamura Y;Takano A;Kato H;Murakami S;Higuchi K;Takahashi A;Fujita H;Hara K;Kadowaki T;Tobe K
我们评估了基于14种已确立的2型糖尿病变异的遗传风险评分（GRS）的临床实用性。我们分析了1，487名日本人（724名2型糖尿病患者和763名对照受试者）中HHEX、CDKAL 1、CDKN 2 B、SLC 30 A8、KCNJ 11、IGF 2BP 2、PPARG、TCF 7 L2、FTO、KCNQ 1、IRS-1、GCKR、UBE 2 E2和C2 CD 4 A/B的14个SNP。根据危险等位基因的数量计算GRS，通过计数所有14个SNP（T-GRS）以及11个与β细胞功能相关的SNP（β-GRS），然后评估每个GRS与临床特征之间的关联。在14个SNPs中，4个SNPs与日本人2型糖尿病显著相关（P < 0.0036）。T-GRS与2型糖尿病显著相关（P = 5.9 × 10−21）。在2型糖尿病受试者中，β-GRS与接受胰岛素治疗的个体相关（β = 0.0131，SE = 0.006，P = 0.0431），诊断时年龄（β =-0.608，SE = 0.204，P = 0.0029）、空腹血清C肽水平（β =-0.032，SE = 0.0140，P = 0.022）和C肽指数（β =-0.031，SE = 0.012，P = 0.0125）。我们的数据表明，β-GRS与β细胞功能下降有关，并且可能有助于选择应该接受更积极的β细胞保留治疗的患者。
We evaluated the clinical usefulness of a genetic risk score (GRS) based on 14 well-established variants for type 2 diabetes. We analyzed 14 SNPs at HHEX, CDKAL1, CDKN2B, SLC30A8, KCNJ11, IGF2BP2, PPARG, TCF7L2, FTO, KCNQ1, IRS-1, GCKR, UBE2E2, and C2CD4A/B in 1,487 Japanese individuals (724 patients with type 2 diabetes and 763 control subjects). A GRS was calculated according to the number of risk alleles by counting all 14 SNPs (T-GRS) as well as 11 SNPs related to β-cell function (β-GRS) and then assessing the association between each GRS and the clinical features. Among the 14 SNPs, 4 SNPs were significantly associated with type 2 diabetes in the present Japanese sample (P < 0.0036). The T-GRS was significantly associated with type 2 diabetes (P = 5.9 × 10−21). Among the subjects with type 2 diabetes, the β-GRS was associated with individuals receiving insulin therapy (β = 0.0131, SE = 0.006, P = 0.0431), age at diagnosis (β = −0.608, SE = 0.204, P = 0.0029), fasting serum C-peptide level (β = −0.032, SE = 0.0140, P = 0.022), and C-peptide index (β = −0.031, SE = 0.012, P = 0.0125). Our data suggest that the β-GRS is associated with reduced β-cell functions and may be useful for selecting patients who should receive more aggressive β-cell–preserving therapy.
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评估18种常见遗传变异的综合遗传变异对2型糖尿病风险的综合影响。
影响因子：
7.7
作者：
Lango H;UK Type 2 Diabetes Genetics Consortium;Palmer CN;Morris AD;Zeggini E;Hattersley AT;McCarthy MI;Frayling TM;Weedon MN
通讯作者：
Weedon MN
影响因子：
30.8
作者：
通讯作者：
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影响因子：
7.7
作者：
Takeuchi F;Serizawa M;Yamamoto K;Fujisawa T;Nakashima E;Ohnaka K;Ikegami H;Sugiyama T;Katsuya T;Miyagishi M;Nakashima N;Nawata H;Nakamura J;Kono S;Takayanagi R;Kato N
通讯作者：
Kato N
影响因子：
7.7
作者：
Gloyn, AL;Weedon, MN;Frayling, TM
通讯作者：
Frayling, TM
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：
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