Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients.
Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients.
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DOI：
10.2337/dc07-2248
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发表时间：
2008-10
期刊：
影响因子：
16.2
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Feng Y;Mao G;Ren X;Xing H;Tang G;Li Q;Li X;Sun L;Yang J;Ma W;Wang X;Xu X
本研究的目的是调查遗传变异是否会影响格列齐特在2型糖尿病患者中的降糖疗效。研究设计和方法-在中国的23家医院共纳入了1,268例2型糖尿病患者，这些患者在过去5年内被诊断为糖尿病，并且最近没有接受过降糖治疗。所有患者均服用格列齐特治疗8周。空腹和口服葡萄糖耐量试验2小时血糖，空腹胰岛素和A1 C分别在基线和治疗8周后测量。我们使用两个独立的队列来检测11个候选基因中25个单核多态性与格列齐特抗糖尿病疗效的相关性。使用一般线性回归模型检验与重要协变量校正的相关性。格列齐特治疗8周后，平均空腹血糖（FPG）从基线时的11.1 mmol/l降至7.7 mmol/l。在队列1中，我们对所有25个SNPs进行了基因分型（n = 661），发现ABCC 8基因的Ser 1369 Ala和KCNJ 11基因的rs 5210与FPG降低显著相关（P = 0.002）。我们进一步对队列2（n = 607）中的Ser 1369 Ala进行基因分型，并证实了队列1中确定的相关性。在汇总分析中，格列齐特治疗8周后，与Ser/Ser基因型受试者相比，Ala/Ala基因型受试者的FPG降低幅度大7.7%（P < 0.001），2小时血糖降低幅度大11.9%（P = 0.003），A1 C降低幅度大3.5%（P = 0.06）。结论：在中国2型糖尿病患者的两个独立队列中，我们发现一致的证据表明ABCC 8基因中的Ser 1369 Ala变异体可以影响格列齐特的抗糖尿病疗效。
OBJECTIVE—The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS—After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS—In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.
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影响因子：
16.2
作者：
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通讯作者：
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