共查询到20条相似文献,搜索用时 15 毫秒
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Franks PW Rolandsson O Debenham SL Fawcett KA Payne F Dina C Froguel P Mohlke KL Willer C Olsson T Wareham NJ Hallmans G Barroso I Sandhu MS 《Diabetologia》2008,51(3):458-463
AIMS/HYPOTHESIS: Mutations at the gene encoding wolframin (WFS1) cause Wolfram syndrome, a rare neurological condition. Associations between single nucleotide polymorphisms (SNPs) at WFS1 and type 2 diabetes have recently been reported. Thus, our aim was to replicate those associations in a northern Swedish case-control study of type 2 diabetes. We also performed a meta-analysis of published and previously unpublished data from Sweden, Finland and France, to obtain updated summary effect estimates. METHODS: Four WFS1 SNPs (rs10010131, rs6446482, rs752854 and rs734312 [H611R]) were genotyped in a type 2 diabetes case-control study (n = 1,296/1,412) of Swedish adults. Logistic regression was used to assess the association between each WFS1 SNP and type 2 diabetes, following adjustment for age, sex and BMI. We then performed a meta-analysis of 11 studies of type 2 diabetes, comprising up to 14,139 patients and 16,109 controls, to obtain a summary effect estimate for the WFS1 variants. RESULTS: In the northern Swedish study, the minor allele at rs752854 was associated with reduced type 2 diabetes risk [odds ratio (OR) 0.85, 95% CI 0.75-0.96, p=0.010]. Borderline statistical associations were observed for the remaining SNPs. The meta-analysis of the four independent replication studies for SNP rs10010131 and correlated variants showed evidence for statistical association (OR 0.87, 95% CI 0.82-0.93, p=4.5 x 10(-5)). In an updated meta-analysis of all 11 studies, strong evidence of statistical association was also observed (OR 0.89, 95% CI 0.86-0.92; p=4.9 x 10(-11)). CONCLUSIONS/INTERPRETATION: In this study of WFS1 variants and type 2 diabetes risk, we have replicated the previously reported associations between SNPs at this locus and the risk of type 2 diabetes. 相似文献
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Loeb M Eskandarian S Rupp M Fishman N Gasink L Patterson J Bramson J Hudson TJ Lemire M 《The Journal of infectious diseases》2011,204(7):1031-1037
To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(-5); odds ratio [OR], 0.68 [95% confidence interval {CI}, .56-.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10(-5); OR, 1.47 [95% CI, 1.21-1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10(-4); OR, 0.69 [95% CI, .56-.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease. 相似文献
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Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population 总被引:3,自引:0,他引:3
Furukawa Y Shimada T Furuta H Matsuno S Kusuyama A Doi A Nishi M Sasaki H Sanke T Nanjo K 《The Journal of clinical endocrinology and metabolism》2008,93(1):310-314
CONTEXT: A genome-wide association study in the French population has detected that novel single-nucleotide polymorphisms (SNPs) in the IDE-KIF11-HHEX gene locus and the SLC30A8 gene locus are associated with susceptibility to type 2 diabetes. OBJECTIVE: We investigated whether SNPs in these loci were associated with type 2 diabetes in Japanese. DESIGN: Two SNPs, rs7923837 and rs1111875, in the IDE-KIF11-HHEX gene locus and one SNP, rs13266634, in the SLC30A8 gene locus were genotyped in Japanese type 2 diabetic patients (n = 405) and in nondiabetic control subjects (n = 340) using the TaqMan genotyping assay system. RESULTS: The G allele of rs7923837 was associated with type 2 diabetes [odds ratio 1.66, 95% confidence interval (CI) 1.28-2.15; P = 0.00014], following the same tendency as in the French population of the previous report. Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.57 (95% CI 1.15-2.16; P = 0.0050) and 3.16 (95% CI 1.40-7.16; P = 0.0038) relative to noncarriers. Although the G allele was a major allele (66.5%) in the French population, it was a minor allele (23.8%) in Japanese. The G allele of rs1111875 was also associated with type 2 diabetes (odds ratio 1.42, 95% CI 1.13-1.78; P = 0.0024). Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.31 (95% CI 0.97-1.77; P = 0.0810) and 2.40 (95% CI 1.34-4.32; P = 0.0028) relative to noncarriers. A significant association with type 2 diabetes was not observed for rs13266634. CONCLUSIONS: Polymorphisms in the IDE-KIF11-HHEX gene locus are associated with susceptibility to type 2 diabetes across the boundary of race. 相似文献
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Y. M. Cho T. H. Kim S. Lim S. H. Choi H. D. Shin H. K. Lee K. S. Park H. C. Jang 《Diabetologia》2009,52(2):253-261
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 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated
with GDM in Koreans.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.
Y. M. Cho and T. H. Kim contributed equally to this study. 相似文献
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Hertel JK Johansson S Raeder H Midthjell K Lyssenko V Groop L Molven A Njølstad PR 《Diabetologia》2008,51(6):971-977
Aims/hypothesis Recent genome-wide association studies performed in selected patients and control participants have provided strong support
for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel
loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study).
Methods We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants
(the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes,
measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs.
Results We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06–1.37, p = 0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04–1.25, p = 0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09–1.33, p = 3.9 × 10−4). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99–1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support
for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p = 8.4 × 10−4).
Conclusions/interpretation Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. 相似文献
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Nitz I Fisher E Grallert H Li Y Gieger C Rubin D Boeing H Spranger J Lindner I Schreiber S Rathmann W Gohlke H Döring A Wichmann HE Schrezenmeir J Döring F Illig T 《The Journal of clinical endocrinology and metabolism》2007,92(8):3183-3188
CONTEXT: On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E(2), the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes. OBJECTIVE: The aim of the present study was to investigate whether genetic variants in the PTGES2 gene are associated with type 2 diabetes. RESULTS: Sequencing of the PTGES2 gene revealed one nonsynonymous coding single-nucleotide polymorphism (SNP) (Arg298His, rs13283456) and a previously unknown promoter SNP g.-417G>T. Both SNPs and additional haplotype tagging SNPs (rs884115, rs10987883, rs4837240) were genotyped in a nested case-control study of 192 incident type 2 diabetes subjects and 384 controls (European Prospective Investigation into Cancer and Nutrition-Potsdam). Carriers of the minor allele of Arg298His had a lower risk to develop the disease [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.41-0.97, P = 0.04], compared with homozygous individuals with the common allele. The PTGES2 Arg298His polymorphism was reinvestigated in a population-based cross-sectional study (Cooperative Health Research in the Augsburg Region) consisting of 239 individuals with impaired glucose tolerance, 226 with type 2 diabetes, and 863 normoglycemic controls. In this study population, the Arg298His polymorphism was significantly associated with impaired glucose tolerance (OR 0.68, 95% CI 0.50-0.93, P = 0.007) and type 2 diabetes (OR 0.61, 95% CI 0.43-0.86, P = 0.004). A pooled analysis of data from both study populations revealed reduced risk of type 2 diabetes (OR 0.62, 95% CI 0.47-0.81, P = 0.0005) in PTGES2 298His allele carriers. CONCLUSION: We obtained evidence from two Caucasian study populations that the His298-allele of PTGES2 Arg298His confers to reduced risk of type 2 diabetes. 相似文献
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Variations in the <Emphasis Type="Italic">HHEX</Emphasis> gene are associated with increased risk of type 2 diabetes in the Japanese population 总被引:1,自引:0,他引:1
Horikoshi M Hara K Ito C Shojima N Nagai R Ueki K Froguel P Kadowaki T 《Diabetologia》2007,50(12):2461-2466
Aims/hypothesis Recently, several groups have carried out whole-genome association studies in European and European-origin populations and
found novel type 2 diabetes-susceptibility genes, fat mass and obesity associated (FTO), solute carrier family 30 (zinc transporter), member 8 (SLC30A8), haematopoietically expressed homeobox (HHEX), exostoses (multiple) 2 (EXT2), CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B) and insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), which had not been in the list of functional candidates. The aim of this study was to determine the association between
single nucleotide polymorphisms (SNPs) in these genes and type 2 diabetes in participants from the Japanese population.
Methods Sixteen previously reported SNPs were genotyped in 864 Japanese type 2 diabetes individuals (535 men and 329 women; age 63.1 ± 9.5 years
(mean±SD), BMI 24.3 ± 3.9 kg/m2) and 864 Japanese control individuals (386 men and 478 women; age 69.5 ± 6.8 years, BMI 23.8 ± 3.7 kg/m2).
Results The SNPs rs5015480 [odds ratio (OR) = 1.46 (95% CI 1.20–1.77), p = 2.0 × 10−4], rs7923837 [OR = 1.40 (95% CI 1.17–1.68), p = 2.0 × 10−4] and rs1111875 [OR = 1.30 (95% CI 1.11–1.52), p = 0.0013] in HHEX were significantly associated with type 2 diabetes with the same direction as previously reported. SNP rs8050136 in FTO was nominally associated with type 2 diabetes [OR = 1.22 (95% CI 1.03–1.46), p = 0.025]. SNPs in other genes such as rs7756992 in CDKAL1, rs10811661 in CDKN2B and rs13266634 in SLC30A8 showed nominal association with type 2 diabetes. rs7756992 in CDKAL1 and rs10811661 in CDKN2B were correlated with impaired pancreatic beta cell function as estimated by the homeostasis model assessment beta index (p = 0.023, p = 0.0083, respectively).
Conclusions/interpretation
HHEX is a common type 2 diabetes-susceptibility gene across different ethnic groups.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.
M. Horikoshi and K. Hara contributed equally to this study. 相似文献
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N M G De Silva A Steele B Shields B Knight K Parnell M N Weedon A T Hattersley T M Frayling 《Diabetic medicine》2007,24(10):1067-1072
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目的观察T2DM人群细胞周期蛋白依赖激酶抑制基因2A/B(CDKN2A/B)基因多态性是否与冠心病风险相关,以早期筛查DM人群中冠心病的高危人群。方法对我院因胸痛症状行冠脉造影或冠脉CT检查的T2DM患者,根据冠脉造影或冠脉CT结果分为冠心病组及非冠心病组。冠心病组共220例,非冠心病组共89例。根据Hapmap数据库选取CDKN2A/B共7个单倍型标记的单核苷酸多态性(SNP):CDKN2Ars2811708(G〉T)、rs3088440(A〉G)和rs3731239(C〉T),CDKN2Brs3217986(A〉C)、rs1063192(C〉T)、rs2285327(A〉G)和rs3217992(A〉G)。对所有个体进行PCR扩增并通过RFLP或基因测序方法读取个体的基因型。结果在T2DM人群中,冠心病组中cDKN2Ars2811708的次要等位基因T频率(26.4%)显著高于非冠心病组(17.4%)(P〈0.05),基因型分布在两组问存在显著性差异(P〈0.05),G/T基因型携带者较G/G基因型携带者发生冠心病的风险显著增加(P(0.05),在校正心血管其他风险因素(如性别、年龄、BMI、DM病程、高血压病病史、脂代谢异常病史、吸烟史)后,这种相关性仍然存在(P〈0.01)。结论T2DM人群中,CDKN2A/B基因单核苷酸多态性可能与冠心病的风险相关。 相似文献
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Santiago JL Alizadeh BZ Martínez A Espino L de la Calle H Fernández-Arquero M Figueredo MA de la Concha EG Roep BO Koeleman BP Urcelay E 《Diabetologia》2008,51(9):1653-1658
AIMS/HYPOTHESIS: In the past few years, several genes outside the MHC region have been described as new susceptibility genetic factors to type 1 diabetes. An association between CAPSL-rs1445898 and type 1 diabetes was reported in a large white population and corroborated in a genome-wide analysis, which also found an association with IL7R, which is located adjacent to CAPSL. The aim of this study was to replicate the aforementioned associations in independent cohorts. METHODS: We analysed two CAPSL (rs1010601 and rs1445898) and three IL7R (rs6897932, rs987106 and rs3194051) polymorphisms. All these single nucleotide polymorphisms (SNPs) were genotyped using TaqMan minor groove binder chemistry in 301 unrelated Spanish type 1 diabetes patients and 646 healthy controls. Additionally, the associated CAPSL SNP rs1445898 was genotyped in a Dutch cohort consisting of 429 type 1 diabetes patients and 720 healthy controls. RESULTS: The homozygous mutant genotype of the CAPSL SNP rs1445898 showed a trend towards a protective effect in the overall Spanish cohort (OR [95% CI] 0.70 [0.44-1.09]; p = 0.09) and in the Dutch cohort (OR [95% CI] 0.74 [0.51-1.05]; p = 0.09). Pooling of both cohorts was performed, yielding a statistically significant difference (Mantel-Haenszel OR 0.71; p = 0.005). This protective effect was significantly different in early-onset vs late-onset Spanish patients (OR [95% CI] 0.26 [0.10-0.65]; p = 0.001). Similarly, in the early-onset subgroup, the homozygous mutant genotype of the IL7R SNP rs6897932 showed a similar protective effect (OR [95% CI] 0.18 [0.02-0.94]; p = 0.02). CONCLUSIONS/INTERPRETATION: In summary, we describe an independent replication of the association between the CAPSL-IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetes patients. 相似文献
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Duesing K Fatemifar G Charpentier G Marre M Tichet J Hercberg S Balkau B Froguel P Gibson F 《Diabetologia》2008,51(5):821-826
Aims/hypothesis Genome-wide association studies (GWASs) recently identified common variants in the CDKN2A/CDKN2B region on chromosome 9p as being strongly associated with type 2 diabetes. Since these association signals were not picked
up by the French-Canadian GWAS, we sought to replicate these findings in the French Europid population and to further characterise
the susceptibility variants at this novel locus.
Methods We genotyped 20 single nucleotide polymorphisms (SNPs) spanning the CDKN2A/CDKN2B locus in our type 2 diabetes case-control cohort. The association between CDKN2A/CDKN2B SNPs and quantitative metabolic traits was also examined in the normoglycaemic participants comprising the control cohort.
Results We report replication of the strong association of rs10811661 with type 2 diabetes found in the GWASs (; OR 1.43 [95% CI 1.24–1.64]). The other CDKN2A/CDKN2B susceptibility variant, rs564398, did not attain statistical significance (p = 0.053; OR 1.11 [95% CI 1.00–1.24]) in the present study. We also obtained several additional nominal association signals
(p < 0.05) at the CDKN2A/CDKN2B locus; however, only the rs3218018 result (p = 0.002) survived Bonferroni correction for multiple testing (adjusted p = 0.04).
Conclusions/interpretation Our comprehensive association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant rs10811661 and type 2 diabetes in the French
population. Further genetic and functional studies are required to identify the aetiological variants at this locus and determine
the cellular and physiological mechanisms by which they act to modulate type 2 diabetes susceptibility.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.
K. Duesing and G. Fatemifar contributed equally to this work. 相似文献
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Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy in American Indians. 总被引:1,自引:0,他引:1
J K Wolford K A Yeatts A R Red Eagle R G Nelson W C Knowler R L Hanson 《Diabetic medicine》2006,23(4):367-376
AIMS: The aldose reductase gene (AKR1B1) is a strong candidate for diabetic nephropathy, and the T allele at rs759853 and the Z-2 allele at an [AC]n microsatellite are associated with diabetic kidney disease in some populations. As AKR1B1 is located on 7q35, where we have previously reported linkage to diabetic nephropathy in Pima Indians, this study examined the association of AKR1B1 variants with diabetic nephropathy in this population. METHODS: AKR1B1 variants were identified by sequencing and genotyped using allelic discrimination and pyrosequencing. Genotype distributions were compared between 107 cases with diabetic end-stage renal disease and 108 control subjects with diabetes for > or = 10 years and no evidence of nephropathy, and between 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships. RESULTS: We identified 11 AKR1B1 single nucleotide polymorphisms (SNPs) and the [AC]n microsatellite polymorphism. Three SNPs were rare and two were in 100% genotypic concordance; thus, eight polymorphisms were genotyped. No variant was associated with diabetic kidney disease in the case-control or family-based study. For example, the T allele at rs759853 had an allele frequency of 0.165 in cases and 0.171 in control subjects (OR = 0.96, 95% CI, 0.57-1.59, P = 0.86); in the family study its frequency was 0.140 and 0.169 in affected and unaffected individuals, respectively (OR = 0.90, 95% CI, 0.53-1.54 P = 0.71). Corresponding values for the Z-2 allele at the [AC]n microsatellite were OR = 1.09 (95% CI 0.72-1.66, P = 0.67) and OR = 1.25 (95% CI 0.81-1.95, P = 0.31) in the case-control and family studies, respectively. CONCLUSIONS: Common AKR1B1 polymorphisms are unlikely to be major determinants of diabetic nephropathy in this population. 相似文献
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Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases 总被引:2,自引:0,他引:2
Martínez A Varadé J Márquez A Cénit MC Espino L Perdigones N Santiago JL Fernández-Arquero M de la Calle H Arroyo R Mendoza JL Fernández-Gutiérrez B de la Concha EG Urcelay E 《Arthritis and rheumatism》2008,58(9):2598-2602
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OBJECTIVE: We determined the occurrence of presenting symptoms in patients with different sites of acute myocardial infarction after controlling for age and conventional risk factors. METHODS: Hospital-based study of patients hospitalized because of first anterior (n=731), inferior (n=719) and lateral (n=96) infarction in Clinical Hospital Split between 1990 and 1994. Data form about presenting symptoms and clinical profile was completed for each patient. RESULTS: Anterior infarctions were more often presented by headache (adjusted odds ratio (OR)=1.67, 95% CI=1.06-2.62), weakness (OR=1.60, 95% CI=1.31-1.96), dyspnea (OR=1.40, 95% CI=1.14-1.72), cough (OR=2.24, 95% CI=1.59-3.16), vertigo (OR=2.04, 95% CI=1.40-2.99) and tinnitus (OR=2.09, 95%CI=1.06-4.14). Inferior infarctions were more often associated with epigastric (OR=1.71, 95%CI=1.30-2.24), neck (OR=1.47, 95% CI=1.10-1.98) and jaw pain (OR=2.16, 95% CI=1.42-3.27), sweating (OR=1.56, 95% CI=1.27-1.92), nausea (OR=2.01, 95%CI=l.64-2.46), vomiting (OR=1.55, 95% CI=1.22-1.97), belching (OR=1.57, 95% CI=1.21-2.03) and hiccups (OR=2.88, 95%CI=1.53-5.42). Patients with lateral infarctions were more likely to complain of left arm (OR=1.80, 95% CI=1.07-3.05), left shoulder (OR=1.82, 95% CI=1.19-2.79) and back pain (OR=2.40, 95% CI=1.28-4.46). Pain was less frequently reported by hypercholesterolemic (P=l.4x10(-7)), patients over 70 years (P=0.002), women (P=0.0007) and those with non-triggered infarction (P=0.0009), whereas those over 70 (P=1.7x10(-6)) and men (P=0.0003) were less likely to report other relevant symptoms. CONCLUSIONS: Our study suggests a linkage between different infarction sites and specific groups of symptoms. Furthermore, coronary patients should give their full attention to non-specific symptoms and any kind of discomfort. 相似文献
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Groenewoud MJ Dekker JM Fritsche A Reiling E Nijpels G Heine RJ Maassen JA Machicao F Schäfer SA Häring HU 't Hart LM van Haeften TW 《Diabetologia》2008,51(9):1659-1663
AIMS/HYPOTHESIS: Genome-wide association studies have recently identified novel type 2 diabetes susceptibility gene regions. We assessed the effects of six of these regions on insulin secretion as determined by a hyperglycaemic clamp. METHODS: Variants of the HHEX/IDE, CDKAL1, SLC30A8, IGF2BP2 and CDKN2A/CDKN2B genes were genotyped in a cohort of 146 participants with NGT and 126 with IGT from the Netherlands and Germany, who all underwent a hyperglycaemic clamp at 10 mmol/l glucose. RESULTS: Variants of CDKAL1 and IGF2BP2 were associated with reductions in first-phase insulin secretion (34% and 28%, respectively). The disposition index was also significantly reduced. For gene regions near HHEX/IDE, SLC30A8 and CDKN2A/CDKN2B we did not find significant associations with first-phase insulin secretion (7-18% difference between genotypes; all p > 0.3). None of the variants showed a significant effect on second-phase insulin secretion in our cohorts (2-8% difference between genotypes, all p > 0.3). Furthermore, the gene variants were not associated with the insulin sensitivity index. CONCLUSIONS: Variants of CDKAL1 and IGF2BP2 attenuate the first phase of glucose-stimulated insulin secretion but show no effect on the second phase of insulin secretion. Our results, based on hyperglycaemic clamps, provide further insight into the pathogenic mechanism behind the association of these gene variants with type 2 diabetes. 相似文献
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To assess the association between type 2 diabetes and rs10811661 polymorphism, upstream of CDKN2A/B, a literature-based search was conducted to collect data. The pooled OR (odds ratio) and 95 % confidence intervals (CI) were used to assess the strength of association between rs10811661 polymorphism and type 2 diabetes. OR with 95 % CI were performed for allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. The effect model was used if there was heterogeneity between studies. Funnel plots were used to predict publication bias. 17 studies with 29,990 cases and 40,977 controls were enrolled in this meta-analysis. Significant association was found in all of the four genetic models: allele contrast (OR = 1.21, 95 % CI 1.18–1.24), additive genetic model (OR = 1.51, 95 % CI 1.40–1.63), dominant genetic model (OR = 1.37, 95 % CI 1.28–1.47) and recessive genetic model (OR = 1.25, 95 % CI 1.21–1.29). The meta-analysis indicated that rs10811661 polymorphism was significantly associated with the risk of type 2 diabetes. 相似文献