在患有2型糖尿病的西非人群中进行全基因组搜索，以寻找与肾功能表型的连锁关系。

A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes.

作者信息

Chen Guanjie, Adeyemo Adebowale A, Zhou Jie, Chen Yuanxiu, Doumatey Ayo, Lashley Kerrie, Huang Hanxia, Amoah Albert, Agyenim-Boateng Kofi, Eghan Benjamin A, Okafor Godfrey, Acheampong Joseph, Oli Johnnie, Fasanmade Olufemi, Johnson Thomas, Rotimi Charles

机构信息

National Human Genome Center at Howard University, College of Medicine, Washington, DC 20059, USA.

出版信息

Am J Kidney Dis. 2007 Mar;49(3):394-400. doi: 10.1053/j.ajkd.2006.12.011.

DOI:10.1053/j.ajkd.2006.12.011

PMID:17336700

Abstract

BACKGROUND

Reduced renal function often is a major consequence of diabetes and hypertension. Although several indices of renal function (eg, creatinine clearance) are clearly heritable and show linkage to several genomic regions, the specific underlying genetic determinants are still being sought. The purpose of this study is to conduct a genome-wide search for regions linked to 3 renal function phenotypes, serum creatinine, creatinine clearance, and glomerular filtration rate (GFR), in persons with type 2 diabetes.

METHODS

A genome-wide panel of 372 autosomal short tandem repeat markers at an average spacing of 9 centimorgan were typed in 691 patients with type 2 diabetes (321 sib pairs and 36 half-sib pairs) in an affected sib pair study in West Africa. Linkage analysis was conducted with the 3 phenotypes by using a multipoint variance components linkage method.

RESULTS

Creatinine clearance showed higher logarithm of odds (LOD) score than the other 2 phenotypes. Linkage to creatinine clearance was observed on chromosomes 16 (marker D16S539, LOD score of 3.56, empirical P = 0.0001), 17 (D17S1298, LOD score of 2.08, empirical P = 0.0018), and 7 (D7S1818, LOD score of 1.84, nominal P = 0.00181, empirical P = 0.0022). Maximum LOD scores for serum creatinine were observed on chromosomes 10 (D10S1432, LOD score of 2.53, empirical P = 0.0001) and 3 (D3S2418, LOD score of 2.21, empirical P = 0.0003) and for GFR on chromosomes 6 (D6S1040, LOD score of 2.08, empirical P = 0.0001) and 8 (D8S256, LOD score of 1.80, empirical P = 0.0001). Several of these results are replications of significant findings from other genome scans.

CONCLUSION

A genome-wide scan for serum creatinine, creatinine clearance, and GFR in a West African sample showed linkage regions that may harbor genes influencing variation in these phenotypes. Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26).

摘要

背景

肾功能减退常常是糖尿病和高血压的一个主要后果。尽管若干肾功能指标（如肌酐清除率）具有明显的遗传性，并且显示与多个基因组区域存在连锁关系，但仍在寻找具体的潜在遗传决定因素。本研究的目的是在2型糖尿病患者中进行全基因组搜索，以寻找与3种肾功能表型（血清肌酐、肌酐清除率和肾小球滤过率（GFR））相关的区域。

方法

在西非进行的一项受累同胞对研究中，对691例2型糖尿病患者（321对同胞对和36对半同胞对）进行了全基因组检测，检测了平均间距为9厘摩的372个常染色体短串联重复标记。通过使用多点方差成分连锁法对这3种表型进行连锁分析。

结果

肌酐清除率显示出比其他2种表型更高的优势对数（LOD）得分。在16号染色体（标记D16S539，LOD得分为3.56，经验性P = 0.0001）、17号染色体（D17S1298，LOD得分为2.08，经验性P = 0.0018）和7号染色体（D7S1818，LOD得分为1.84，名义P = 0.00181，经验性P = 0.0022）上观察到与肌酐清除率的连锁关系。血清肌酐的最高LOD得分在10号染色体（D10S1432，LOD得分为2.53，经验性P = 0.0001）和3号染色体（D3S2418，LOD得分为2.21，经验性P = 0.0003）上，而GFR的最高LOD得分在6号染色体（D6S1040，LOD得分为2.08，经验性P = 0.0001）和8号染色体（D8S256，LOD得分为1.80，经验性P = 0.0001）上。这些结果中有几个是其他全基因组扫描中显著发现的重复。