Polymorphisms of GLP-1 Receptor Gene and Response to GLP-1 Analogue in Patients with Poorly Controlled Type 2 Diabetes

Journal of Diabetes Research - Tập 2015 - Trang 1-10 - 2015
Chia-Hung Lin1,2, Yun‐Shien Lee3,4, Yu‐Yao Huang1, Sheng-Hwu Hsieh1, Zih-Syuan Chen2, Chi‐Neu Tsai2
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan
3Department of Biotechnology, Ming Chuan University, Taoyuan 333, Taiwan
4Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

Tóm tắt

Aim. The relationship between genetic polymorphisms of the glucagon-like peptide-1 (GLP-1) receptor (GLP1R) gene and unresponsiveness to GLP-1 analogue treatment in patients with poorly controlled type 2 diabetes mellitus (DM) is unclear.Methods. Thirty-six patients with poorly controlled type 2 DM were enrolled and they received six days of continuous subcutaneous insulin infusion for this study. After the normalization of blood glucose in the first 3 days, the patients then received a combination therapy with injections of the GLP-1 analogue, exenatide, for another 3 days. All 13 exons and intron-exon boundaries of theGLP1Rgene were amplified to investigate the association.Results. The short tandem repeat at 8GA/7GA (rs5875654) had complete linkage disequilibrium (LD, withr2=1) with single nucleotide polymorphism (SNP) rs761386. Quantitative trait loci analysis ofGLP1Rgene variation with clinical response of GLP1 analogue showed the missense rs3765467 and rs761386 significantly associated with changes in the standard deviation of plasma glucose (SDPGbaseline-SDPGtreatment with GLP-1 analogue) (P=0.041and 0.019, resp.). The reportedPvalues became insignificant after multiple testing adjustments.Conclusion. The variable response to the GLP-1 analogue was not statistically correlated with polymorphisms of theGLP1Rgene in patients with poorly controlled type 2 DM.

Từ khóa


Tài liệu tham khảo

10.1053/j.gastro.2007.03.054

1994, The Journal of Biological Chemistry, 269, 18827, 10.1016/S0021-9258(17)32241-X

10.1016/s0140-6736(06)69705-5

10.1210/jc.87.3.1282

10.1331/japha.2012.10217

10.2337/db08-1589

10.1007/s00125-009-1344-5

10.1007/s00125-007-0753-6

10.2337/db11-1732

1994, Zeitschrift fur Gastroenterologie, 32, 203

10.1073/pnas.1218051109

10.1016/j.regpep.2005.05.001

10.1056/nejme0810630

10.2337/dc10-0200

10.1016/j.clinthera.2007.12.013

10.2337/diacare.22.9.1462

10.1007/bf00280883

2002, Postgraduate Medicine, 111, 69, 10.3810/pgm.2002.05.1200

10.1507/endocrj.EJ11-0036

10.1016/j.diabres.2004.02.004

10.1100/2012/365104

10.2337/dc09-2191

10.7326/0003-4819-154-2-201101180-00300

10.2337/dc06-2532

10.1124/mol.111.072884

10.1007/s00125-009-1307-x

10.1016/s0167-0115(03)00120-4

10.1210/en.142.10.4462

10.1074/jbc.m111.276808

Thông tin
Thông tin xuất bản

Journal of Diabetes Research

Tập 2015

1-10

Thông tin tác giả