A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes
A genome-wide search for linkage to renal function phenotypes in West Africans with type 2 diabetes
复制标题
DOI：
10.1053/j.ajkd.2006.12.011
复制
发表时间：
2007-03-01
影响因子：
13.2
通讯作者：
Rotimi, Charles
中科院分区：
文献类型：
--
作者：
Chen, Guanjie;Adeyemo, Adebowale A.;Rotimi, Charles
背景：肾功能下降通常是糖尿病和高血压的主要后果。虽然肾功能的几个指标（如肌酐清除率）是明确的遗传，并显示与几个基因组区域的联系，具体的潜在遗传决定因素仍在寻找。本研究的目的是在2型糖尿病患者中进行全基因组搜索与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。对691例2型糖尿病患者的372个常染色体短串联重复序列标记进行了基因分型，平均间隔为9厘摩（321个同胞对和36个半同胞对）在西非受影响的同胞对研究。采用多点方差分量连锁法对3种表型进行连锁分析。结果：肌酐清除率的比值对数（LOD）得分高于其他2种表型。在16号染色体（标记物D16 S539，LOD评分为3.56，经验P = 0.0001）、17号染色体（D17 S198，LOD评分为2.08，经验P = 0.0018）和7号染色体（D 7S 1818，LOD评分为1.84，标称P = 0.00181，经验P = 0.0022）上观察到与肌酐清除率的关联。在10号染色体上观察到血清肌酐的最大LOD评分（D10 S1432，LOD评分为2.53，经验P = 0.0001）和3（D3 S2418，LOD评分为2.21，经验P = 0.0003）和6号染色体上的GFR（D 6S 1040，LOD评分为2.08，经验P = 0.0001）和8（D8 S256，LOD评分为1.80，经验P = 0.0001）。这些结果中有几个是从其他基因组scannes.Conclusion显着的发现复制：全基因组扫描血清肌酐，肌酐清除率，GFR在西非样本显示连锁区域，可能窝藏基因影响这些表型的变化。这些区域中与糖尿病肾病和/或高血压模型中的肾损伤有关的潜在候选基因包括CYBA（或P22 PHOX）（16 q24）、NOX 1（10 q22）和NOX 3（6q25.1-q26）。
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 (D17S198, 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).