Replication of association between polymorphisms of the pancreatic ATP-sensitive potassium channel and susceptibility to type 2 diabetes in two Russian urban populations

Chistiakov, Dimitry A.; Потапов, В. А.; Khodirev, Dmitry S.; Шамхалова, Минара Шамхаловна; Shestakova, Marina Vladimirovna; Носиков, В. В.

doi:10.2478/s11535-009-0059-4

Cited by 5 publications

(2 citation statements)

References 39 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We did not include the Utahand U.K. samples from Inoue et al [ 14 ] because p.E23K failed to meet HWE in the control group (p = 0.002 and p = 0.04, respectively). Results from both studies with Russian samples were excluded because in one study, rs5219 failed to obey HWE in T2DM (p = 0.0002) and control (p = 2 x 10 –8 ) groups, and in the other study the control group failed to meet this criterion (p = 0.02) [ 12 , 15 ]. Results from Koo et al [ 16 ] were excluded because control group genotypes reached borderline significance for HWE (p = 0.05), and the results of Sale et al [ 17 ] were also excluded because rs5219 (p = 0.0009) deviated from HWE proportions in African-American patients.…”

Section: Resultsmentioning

confidence: 99%

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

et al. 2015

View full text Add to dashboard Cite

The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes mellitus (T2DM) research over the past two decades. It has been hypothesized that the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8) variant may be a causal factor in the disease; therefore, in this study we performed a meta-analysis to evaluate the association between these single nucleotide polymorphisms (SNPs), including our original data on the Siberian population (1384 T2DM and 414 controls). We found rs5219 and rs757110 were not associated with T2DM in this population, and that there was linkage disequilibrium in Siberians (D’=0.766, r2= 0.5633). In addition, the haplotype rs757110[T]-rs5219[C] (p.23K/p.S1369) was associated with T2DM (OR = 1.52, 95% CI: 1.04-2.24). We included 44 original studies published by June 2014 in a meta-analysis of the p.E23K association with T2DM. The total OR was 1.14 (95% CI: 1.11-1.17) for p.E23K for a total sample size of 137,298. For p.S1369A, a meta-analysis was conducted on a total of 10 studies with a total sample size of 14,136 and pooled OR of 1.14 [95% CI (1.08-1.19); p = 2 x 10-6]. Our calculations identified causal genetic variation within the ABCC8/KCNJ11 region for T2DM with an OR of approximately 1.15 in Caucasians and Asians. Moreover, the OR value was not dependent on the frequency of p.E23K or p.S1369A in the populations.

show abstract

Section: Resultsmentioning

confidence: 99%

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…По данным этих ис следований, проведенных в разных этнических популя-циях, выявлена ассоциация полиморфного маркера Glu23Lys гена KCNJ11 с СД-2 [8][9][10][16][17][18].…”

Section: Discussionunclassified

Association of the polymorphic marker Glu23Lys in the KCNJ11 gene with hypertension in Kyrgyz patients

Isakova¹,

Talaibekova²,

Asambaeva³

et al. 2017

Terapevticheskii arkhiv

View full text Add to dashboard Cite

РезюмеЦель исследования. Изучить ассоциацию полиморфного маркера Glu23Lys гена KCNJ11 с развитием артериальной гипер-тонии (АГ) у пациентов киргизской национальности. Материалы и методы. Исследование случай-контроль включало 214 неродственных этнических киргизов, из которых в основную группу вошли 152 больных АГ (82 мужчин и 70 женщин), контрольную группу составили 109 условно здоровых лиц (61 мужчина и 48 женщин). Средний возраст обследованных достигал 55,2±10,1 года. АГ верифицировали при повы-шении артериального давления (АД) более 140/90 мм рт.ст. Идентификации аллельных вариантов полиморфного маркера Glu23Lys гена KCNJ11 осуществляли методом анализа полиморфизма длин рестрикционных фрагментов (ПДРФ). Результаты. Распространенность 3 генотипов (Glu23Glu, Glu23Lys и Lys23Lys) полиморфизма Glu23Lys гена KCNJ11 у больных АГ и контрольной группы существенно различалась (χ 2 =8,04; р=0,018). Генотипы Lys23Lys и Glu23Lys статисти-чески значимо чаще регистрировались в группе с АГ, а гомозиготный генотип Glu23Glu, напротив, чаще встречался в контрольной группе, чем в основной. Распространенность аллеля 23Lys в группе с АГ статистически значимо выше, чем в контроле (χ 2 =7,36; р=0,0067). Носительство аллеля 23Lys повышало риск развития АГ в 1,68 раза (отношение шансов -ОШ 1,68 при 95% доверительном интервале -ДИ от 1,17 до 2,41), носительство аллеля Glu23, напротив, оказывало протективное действие (ОШ 0,60 при 95% ДИ от 0,41 до 0,86). Заключение. У киргизов полиморфный маркер Glu23Lys гена KCNJ11 ассоциирован с АГ. Маркером повышенного риска развития АГ является аллель 23Lys. Aim. To study the association of the polymorphic marker Glu23Lys in the KCNJ11 with the development of hypertension in Kyrgyz patients. Subjects and methods. This case-control study enrolled 214 unrelated ethnic Kyrgyzes, in which a study group included 152 hypertensive patients (82 men and 70 women) and a control group consisted of 109 apparently healthy individuals (61 men and 48 women). The examinees' mean age was 55.2±10.1 years. Hypertension was verified when blood pressure (BP) was above 140/90 mm Hg. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify the polymorphic marker Glu23Lys in the KCNJ11 gene. Results. In the hypertension and control groups, the prevalence of 3 genotypes (Glu23Glu, Glu23Lys, and Lys23Lys) of the Glu23Lys polymorphism in the KCNJ11 gene differed significantly (χ 2 =8.04; p=0.018). The Lys23Lys and Glu23Lys genotypes were statistically more frequently recorded in the hypertension group and the homozygous Glu23Glu genotype was, on the contrary, more common in the control group than in the study one. In the hypertension group, the 23Lys allele frequency was statistically significantly higher than that in the control one (χ 2 =7.36; p=0.0067). The carriage of the 23Lys allele increased the risk of hypertension by 1.68 times (odds ratio (OR), 1.68; 95% confidence interval (CI), 1.17-2.41), that of the Glu23 allele had, on the contrary, a protective effect (OR, 0.60; 95% CI, ...

show abstract

The carriage of risk variants of CDKAL1 impairs beta-cell function in both diabetic and non-diabetic patients and reduces response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel

et al. 2011

View full text Add to dashboard Cite

On chromosome 6q22.3, a cluster of single-nucleotide polymorphisms located in intron 5 of the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) gene were shown to confer susceptibility to type 2 diabetes in multiple ethnic groups. The diabetogenic role of CDKAL1 variants is suggested to consist in lower insulin secretion probably due to the insufficient inhibition of the CDK5 activity. In this study, we assessed the association of several SNPs of CDKAL1 with T2D in 772 Russian affected patients and 773 normoglycemic controls using a Taqman-based allelic discrimination assay. We showed association of the minor allele C of rs10946398 (Odds Ratio (OR) = 1.21, 95% CI = 1.04-1.4, P = 0.016), allele C of rs7754840 (OR = 1.18, 95% CI = 1.01-1.37, P = 0.038), and allele G of rs7756992 (OR = 1.21, 95% CI = 1.04-1.42, P = 0.017) with higher diabetes risk thereby replicating the predisposing role of CDKAL1 in etiology of T2D. These alleles contribute to three haplotypes (CCA, CGG, and CCG) related to higher diabetes risk (OR = 1.48, 2.12, and 1.95). Combinations of these haplotypes between each other form the group of high-risk haplogenotypes whose carriers had decreased HOMA-β compared to other CDKAL1 variants in both diabetic (38.6 ± 19.3 vs. 48.2 ± 21.2, P(adjusted) = 0.019-0.044) and non-diabetic (91.8 ± 42.1 vs. 108 ± 47.2, P(adjusted) = 0.0054-0.01) patients. The carriage of the risk haplogenotypes of CDKAL1 was associated with reduced response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel. These data suggest that CDKAL1 is involved in the pathogenesis of T2D through impaired beta-cell function.

show abstract

Replication of association between polymorphisms of the pancreatic ATP-sensitive potassium channel and susceptibility to type 2 diabetes in two Russian urban populations

Cited by 5 publications

References 39 publications

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

Association of the polymorphic marker Glu23Lys in the KCNJ11 gene with hypertension in Kyrgyz patients

The carriage of risk variants of CDKAL1 impairs beta-cell function in both diabetic and non-diabetic patients and reduces response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel

Contact Info

Product

Resources

About