Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin.

Rissanen, Johanna; Markkanen, A; Kärkkäinen, Päivi; Pihlajamäki, Jussi; Kekäläinen, Päivi; Mykkänen, Leena; Kuusisto, Johanna; Karhapää, Pauli; Niskanen, Leo; Laakso, Markku

doi:10.2337/diacare.23.1.70

Cited by 82 publications

(57 citation statements)

References 11 publications

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“…Florez et al (6) found the Ala/Ala carriers had a significantly lower insulin index, i.e., insulin secretion function, compared with Ser/Ser carriers in subjects with impaired glucose tolerance. However, other studies did not find any association between the Ser1369Ala variant and insulin secretion in nondiabetic subjects (19,20). We also did not find any association between the Ser1369Ala variant and fasting plasma insulin level or HOMA-B, an indicator for insulin secretion, either at baseline or after gliclazide treatment.…”

Section: Data Collection and Clinical Laboratory Methodsmentioning

confidence: 38%

Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients

et al. 2008

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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 ϭ 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P ϭ 0.002). We further genotyped Ser1369Ala in cohort 2 (n ϭ 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 Ͻ 0.001), an 11.9% greater decrease in 2-h plasma glucose (P ϭ 0.003), and a 3.5% greater decrease in A1C (P ϭ 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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Section: Data Collection and Clinical Laboratory Methodsmentioning

confidence: 38%

Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients

et al. 2008

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“…Several studies have examined candidate genes in women with and without GDM. Positive associations were shown for genes encoding glucokinase [11], calpain-10 [12], sulfonylurea receptor 1 [13], potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) [14], β 3 adrenergic receptor [15], plasminogen activator inhibitor 1 [16] and transcription factor 7-like 2 (TCF7L2) [17,18]. Except for the effects of TCF7L2 in Scandinavian women [17], no robust associations of genetic variants with GDM have been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

et al. 2008

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Aims/hypothesis New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). Methods The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A−CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. Results Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p=4.17×10 −9 ) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p=1.05×10 −7 ) in the CDKN2A−CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p=0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p=0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p=0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p=0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. Conclusions/interpretation Some of the type 2 diabetesassociated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.

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“…Recently, the association of the T110I polymorphism in SLC2A2 with the risk of type 2 diabetes among Finnish subjects was replicated (50). The results of other case control studies with respect to SNPs in SLC2A2 and ABCC8 and risk of type 2 diabetes have, however, been inconsistent (1,2,13,15,32,34,36,39,40,43,47), whereas a meta-analysis confirmed the association of the K allele of the E23K polymorphism in KCNJ11with an increased risk of type 2 diabetes among Caucasians (47). The prospective DPP, however, unexpectedly found a lower risk of conversion from IGT to type 2 diabetes in the carriers of the K allele (14).…”

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confidence: 97%

Physical activity modifies the effect of SNPs in theSLC2A2(GLUT2) andABCC8(SUR1) genes on the risk of developing type 2 diabetes

Kilpeläinen

Lakka

Laaksonen

et al. 2007

Physiological Genomics

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-Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N ϭ 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6-to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P ϭ 0.022-0.027 for the SNPs in SLC2A2, and P ϭ 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT. sulphonylurea receptor-1; glucose transporter-2; impaired glucose tolerance; exercise; single nucleotide polymorphism GENETIC FACTORS AND LIFESTYLE interact in the development of type 2 diabetes. Physical activity, favorable dietary changes, and weight reduction were essential components of a successful lifestyle intervention in two large randomized controlled trials on the prevention of type 2 diabetes in high-risk individuals with impaired glucose tolerance (IGT), including the Finnish Diabetes Prevention Study (DPS) (44) and the Diabetes Prevention Program (DPP) (22). In the DPS, increased physical activity was associated with a decreased risk of type 2 diabetes independently of changes in diet and body weight. The individuals who increased their physical activity most (i.e., were in the upper third of the change) were 66% less likely to develop type 2 diabetes than those in the lower third (24).Two major pathogenetic factors leading to type 2 diabetes are insulin resistance and impaired insulin secretion (7). Thus the reduction in the risk of type 2 diabetes with physical activity may occur by an improvement in insulin sensitivity, ␤-cell function, or both. Numerous exercise-training studies have demonstrated that physical activity increases insulin sensitivity (18). The effect of physical activity on ␤-cell function is less clear, but some studies suggest that increased physical activity may improve early insulin secretion independently of insulin resistance (5, 11).Glucose transporter-2 (GLUT2), encoded by the SLC2A2 gene, is a facilitative glucose transporter t...

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Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin.

Cited by 82 publications

References 11 publications

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

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

Physical activity modifies the effect of SNPs in theSLC2A2(GLUT2) andABCC8(SUR1) genes on the risk of developing type 2 diabetes

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