一项针对2型糖尿病的德国全基因组连锁扫描支持1号染色体p36.13区域存在一个代谢综合征位点以及16号染色体p12.2区域存在一个2型糖尿病位点。
A German genome-wide linkage scan for type 2 diabetes supports the existence of a metabolic syndrome locus on chromosome 1p36.13 and a type 2 diabetes locus on chromosome 16p12.2.
作者信息
Hoffmann K, Mattheisen M, Dahm S, Nürnberg P, Roe C, Johnson J, Cox N J, Wichmann H E, Wienker T F, Schulze J, Schwarz P E, Lindner T H
机构信息
Institute of Medical Genetics, Charité, University Medical School, Humboldt University, Berlin, Germany.
出版信息
Diabetologia. 2007 Jul;50(7):1418-22. doi: 10.1007/s00125-007-0658-4. Epub 2007 Apr 27.
AIMS/HYPOTHESIS: The aim was to identify type 2 diabetes susceptibility regions in 250 German families.
SUBJECTS AND METHODS
We conducted a genome-wide linkage scan using 439 short tandem repeat polymorphisms at an average resolution of 7.76 +/- 3.80 cM (Marshfield). In an affected-only-design (affected sib pairs), we performed nonparametric multipoint linkage analyses. Conditional analyses were applied where linkage signals were found in the baseline analyses.
RESULTS
We identified two loci with nominal evidence for linkage on chromosomes 1p36.13 and 16p12.2 (D1S3669, 37.05 cM, logarithmic odds ratio [LOD] = 1.49, p = 0.004; D16S403, 43.89 cM, LOD = 1.85, p = 0.002). D16S403 crossed the empirically obtained threshold of genome-wide suggestive significance of LOD = 1.51. Positive findings in those regions have been reported by the following other linkage studies on: (1) symptomatic/clinical gall bladder disease with type 2 diabetes in Mexican Americans from the San Antonio Family Diabetes/Gallbladder Study (LOD = 3.7, D1S1597-D1S407, 29.93-33.75 cM); (2) body size-adiposity in another Mexican American population (D1S1597, LOD = 2.53, 29.93 cM); (3) lipid abnormalities (LOD = 3.1, D1S2826-D1S513, 41.92-60.01 cM); and (4) hypertension in Australian sib pairs (LOD = 3.1, D1S2834-D1S2728, 31.02-33.75 cM); as well as (5) a meta-analysis of four European type 2 diabetes-related genome scans (LOD = 1.09, D16S412, 42.81 cM). In linkage analyses conditional on evidence for linkage at D16S403 we identified a LOD increase (Delta LOD) of 1.55 (p = 0.0075) at D17S2180. Similar conditioning on D17S2180 revealed evidence for interaction with D1S3669 (Delta LOD = 1.67, p = 0.0055), D16S403 (Delta LOD = 1.48, p = 0.0091) and another locus on chromosome 1 where several genome scans have reported evidence for linkage ( approximately 200 cM, Delta LOD = 1.60, p = 0.0066).
CONCLUSIONS/INTERPRETATION: Our results and the findings of other studies are consistent with the presence of a locus for a complex metabolic syndrome on chromosome 1p36.13.
目的/假设：目的是在250个德国家庭中确定2型糖尿病易感性区域。
对象与方法
我们使用439个短串联重复多态性进行全基因组连锁扫描，平均分辨率为7.76±3.80厘摩（马什菲尔德）。在仅患病例设计（患病同胞对）中，我们进行了非参数多点连锁分析。在基线分析中发现连锁信号的地方应用条件分析。
结果
我们在1号染色体p36.13和16号染色体p12.2上确定了两个有连锁名义证据的位点（D1S3669，37.05厘摩，对数优势比[LOD]=1.49，p=0.004；D16S403，43.89厘摩，LOD=1.85，p=0.002）。D16S403超过了经验性获得的全基因组提示性显著水平阈值LOD=1.51。以下其他连锁研究在这些区域报告了阳性结果：（1）来自圣安东尼奥家族糖尿病/胆囊研究的墨西哥裔美国人中伴有2型糖尿病的症状性/临床胆囊疾病（LOD=3.7，D1S1597-D1S407，29.93-33.75厘摩）；（2）另一个墨西哥裔美国人群中的体型-肥胖（D1S1597，LOD=2.53，29.93厘摩）；（3）脂质异常（LOD=3.1，D1S2826-D1S513，41.92-60.01厘摩）；以及（4）澳大利亚同胞对中的高血压（LOD=3.1，D1S2834-D1S2728，31.02-33.75厘摩）；还有（5）四项欧洲2型糖尿病相关全基因组扫描的荟萃分析（LOD=1.09，D16S412，42.81厘摩）。在以D16S403的连锁证据为条件的连锁分析中，我们在D17S2180处确定LOD增加（ΔLOD）为1.55（p=0.0075）。以D17S2180为类似条件揭示了与D1S3669（ΔLOD=1.67，p=0.0055）、D16S403（ΔLOD=1.48，p=0.0091）以及1号染色体上另一个位点相互作用的证据，几项全基因组扫描在该位点报告了连锁证据（约200厘摩，ΔLOD=1.60，p=0.0066）。
结论/解读：我们的结果以及其他研究的发现与1号染色体p36.13上存在一个复杂代谢综合征位点一致。
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