Human Genetics (Impact Factor: 4.82). 07/2000; 107(2):138-144. DOI: 10.1007/s004390000345
The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGGMAGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. Here, we have investigated the association of this SNP with type 2 diabetes mellitus (T2DM) in French Caucasian subjects. We have observed an increased frequency of the A allele (37.1% vs 27.6%, P=0.0048; odds ratio 1.54), of the AA genotype (15.7% vs 9.8%; P=0.025), and of the combined AA/AG genotypes (58.5% vs 45.5%, P=0.0098; odds ratio 1.69) in patients compared with controls. This association is stronger in the subgroup of patients with age of diagnosis of diabetes equal to or less than 45 years: A allele 43.2% (P=0.0003 compared with controls; odds ratio 1.99), AA genotype 21.4% (P=0.0032), and combined AA/AG genotypes 65.1% (P=0.0022; odds ratio 2.23). Unexpectedly, the G allele is strongly associated with arterial hypertension in obese diabetic subjects (GG vs AA odds ratio 19.97). In conclusion, we have observed an association of an SNP in exon 31 of the SUR1 gene with T2DM. These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene.
"Furthermore, a large-scale meta-analysis of the data for the G716V and T759T markers yielded negative results . Compared to these markers, a silent G-to-A nucleotide substitution in codon 1273 (R1273R; rs1799859) located in exon 31 of ABCC8 was assessed less frequently but showed consistent association with T2D    and diabetesrelated traits   in several populations. Although T2D is a heterogeneous collection of metabolic syndromes, defects in β-cell function seem to play a major role in T2D etiology because the majority of genetic variants conferring susceptibility to this pathology are involved in control of β-cell development and function . "
[Show abstract][Hide abstract] ABSTRACT: The KCNJ11 and ABCC8 genes encode components of the pancreatic ATP-sensitive potassium (KATP) channel. Previously, we reported
association of the KCNJ11 E23K and ABCC8 R1273R G/A variants with type 2 diabetes (T2D) in a small Russian population sample
(n=244). Here we replicated association between these genetic variants and T2D in a larger cohort (588 diabetic and 597 non-diabetic
subjects). Using the ANCOVA analysis, Odds Ratios (ORs) and relationships between the carriage of a genotype and biochemical
parameters of the patients were assessed and then adjusted for confounders (age, gender, HbA1c, hypertension, and obesity).
The KCNJ11 K23 variant and the ABCC8 R1273R allele A showed association with higher risk of T2D (adjusted OR of 1.41 and 2.03,
P<0.0001, respectively). Diabetic patients homozygous for K/K had lower 2h insulin (Padjusted=0.044). The ABCC8 A/A variant was associated with increased 2h serum insulin in diabetic and non-diabetic subjects (Padjusted=0.027 and 0.033, respectively). The carriage of the risk variant K/K of KCNJ11 E23K or A/A of ABCC8 G/A R1273R was associated
with reduced response to nonsulfonylurea and sulfonylurea blockers of the pancreatic KATP channel. Adjusted attributable population
risk was 3.0% (KCNJ11 E23K) and 4.8% (ABCC8 G/A) suggesting for the modest effects of these genetic variants on diabetes susceptibility.
Central European Journal of Biology 02/2009; 5(1):67-77. DOI:10.2478/s11535-009-0059-4 · 0.71 Impact Factor
"Investigations using genome scan approaches have found novel genetic loci associated with CAD, which might provide additional insight to genetic factors contributing to atherosclerosis and coronary events     . There also are numerous studies that have found genetic associations or linkage with related disorders, such as hypertension      , obesity         , diabetes           , lipids    , and oxidative stress . "
[Show abstract][Hide abstract] ABSTRACT: Individuals with genetic predisposition to atherosclerosis have an increased risk for developing coronary artery disease (CAD), especially at young ages. They may derive the greatest benefit from traditional preventive strategies and strategies targeting novel,emerging risk factors. Because CAD is a complex, multifactorial disorder, global risk assessment has been recognized as an effective approach in preventing CAD and its manifestations. The systematic collection and interpretation of family history information is currently the most appropriate screening approach to identify individuals with genetic susceptibility to CAD. Much of the familial aggregation of CAD might be explained by familial aggregation of established risk factors and emerging CAD risk factors. Tests to assess genetic risk for CAD are primarily biochemical analyses that measure the different pathways involved in development and progression of disease. Some of these can guide and explain responses to treatment.
Primary Care Clinics in Office Practice 10/2004; 31(3):711-37, xi-xii. DOI:10.1016/j.pop.2004.04.001 · 0.74 Impact Factor
"Mutations and deficiencies in this protein were detected in patients with hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high insulin secretion (Thomas et al. 1995; Nestorowicz et al. 1996, 1998; Glaser et al. 1999; Verkarre et al. 1998). An arginine residue at codon 1273 was reported to be associated with hyperinsulinemia in Mexican American nondiabetic individuals (Goksel et al. 1998) and with type 2 diabetes mellitus in French Caucasians (Reis et al. 2000). ABCC9 (SUR2) is the primary regulatory subunit expressed in muscle cells and generates two splice variants, SUR2A (exon 38a) and SUR2B (exon 38b) (Isomoto et al. 1996). "
[Show abstract][Hide abstract] ABSTRACT: We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in eight genes encoding the ATP-binding
cassette, subfamily C (ABCC/MRP/CFTR), by direct sequencing of their entire genomic regions, except repetitive sequence elements. This approach identified 688
SNPs and 91 insertion/deletion polymorphisms among the eight genes. Of the 688 SNPs, 81 were identified in the ABCC1 gene, 41 in ABCC2, 30 in ABCC3, 230 in ABCC4, 76 in ABCC5, 58 in CFTR, 102 in ABCC8, and 70 in ABCC9. Six SNPs were located in the 5′ flanking regions, 617 in introns, 46 in exons, and 19 in the 3′ flanking regions. These
variants should contribute to studies that investigate possible correlations of genotypes with disease-susceptibility phenotypes
and responsiveness or adverse effects to drugs.
Journal of Human Genetics 01/2002; 47(4):147-171. DOI:10.1007/s100380200018 · 2.46 Impact Factor
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