Abstract:
OBJECTIVES:High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-term efficiency. DESIGN:102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months. METHODS:Most significant hits were analyzed in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25 healthy nondiabetic volunteers was conducted to investigate the effects of identified polymorphisms. RESULTS:In the discovery group of 102 patients, minor alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally associated with metformin inefficiency (P = 1.9 × 10-6 to 8.1 × 10-6). Effects of rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from Slovakia alone, whereas rs7757336 was significantly associated with a reduced metformin response in combined group. In pharmacokinetic study, group of individuals harboring risk alleles of rs7757336 and rs2481030 displayed significantly reduced AUC∞ of metformin in plasma. CONCLUSIONS:For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5' flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5' flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Zaharenko L,Kalnina I,Geldnere K,Konrade I,Grinberga S,Židzik J,Javorský M,Lejnieks A,Nikitina-Zake L,Fridmanis D,Peculis R,Radovica-Spalvina I,Hartmane D,Pugovics O,Tkáč I,Klimčáková L,Pīrāgs V,Klovins Jdoi
10.1530/EJE-16-0347subject
Has Abstractpub_date
2016-12-01 00:00:00pages
531-540issue
6eissn
0804-4643issn
1479-683Xpii
EJE-16-0347journal_volume
175pub_type
杂志文章abstract:OBJECTIVE:Chronic exposure to elevated glucocorticoid (GC) concentrations induces detrimental effects in several tissues. In the skin, GCs provoke intense alterations on various parameters of the physiology of fibroblasts, cumulatively leading to skin atrophy and impaired wound healing. As there are concerns that GCs m...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.01913
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:It is well established that ovarian steroids modulate gonadotropin secretion from anterior pituitary cells. It has been speculated that insulin and IGF-I might influence gonadotropin secretion. OBJECTIVE:To investigate the effects of IGF-I and estradiol alone, or combinations of IGF-I with insulin and estra...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1440073
更新日期:2001-01-01 00:00:00
abstract::Little is known about patients with malignant digestive neuroendocrine tumours (MD-NETs). Although their incidence is increasing, MD-NETs remain a rare cancer, representing 1% of digestive cancers. Most MD-NETs are well-differentiated. MD-NET poorly differentiated carcinomas account for 20% of cases on average. Anatom...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-12-0418
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abstract:OBJECTIVE:To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS:Twenty-four women with PCOS, aged 25.4+/-4.3 (mean+/-s.d.) years, body mass index 24...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-02-01 00:00:00
abstract:OBJECTIVE:To assess the performance of current clinical recommendations for the evaluation of an adrenal incidentaloma. DESIGN AND METHODS LITERATURE REVIEW: Electronic databases (Pubmed, Ovid and citation searches from key articles) from 1980 to 2008 were searched. Eligible studies were those deemed most applicable to...
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doi:10.1530/EJE-09-0234
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abstract:OBJECTIVE:Cushing's disease (CD) is usually caused by ACTH-secreting pituitary microadenomas, while silent corticotroph adenomas (SCA) are macroadenomas without Cushingoid features. However, the molecular mechanism(s) underlying their different tumor growth remains unknown. The aim of the current study was to evaluate ...
journal_title:European journal of endocrinology
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abstract::Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation scre...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1530/EJE-12-0333
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journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
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更新日期:2010-08-01 00:00:00
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1440653
更新日期:2001-06-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0173
更新日期:2019-12-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1390424
更新日期:1998-10-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1370200
更新日期:1997-08-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-0160
更新日期:2012-07-01 00:00:00
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1500649
更新日期:2004-05-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
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journal_title:European journal of endocrinology
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更新日期:2010-03-01 00:00:00
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1380337
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1500425
更新日期:2004-04-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02108
更新日期:2006-05-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02015
更新日期:2005-11-01 00:00:00
abstract::It is well known that normal and mildly elevated luteinizing hormone (LH) levels induce increased activity of ovarian 17-hydroxylase and 17,20-lyase, the cytochrome P450cl7alpha (P450) enzymes. This leads to increased ovarian 17alpha-hydroxyprogesterone (17-OHP) and androstenedione production. In contrast, it has been...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1390304
更新日期:1998-09-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1530/eje.1.02226
更新日期:2006-09-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1450295
更新日期:2001-09-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0397
更新日期:2016-10-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
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更新日期:2001-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1530/eje.0.1460209
更新日期:2002-02-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
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更新日期:2016-04-01 00:00:00