African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.
African ancestry allelic variation at the MYH9 gene contributes to increased susceptibility to non-diabetic end-stage kidney disease in Hispanic Americans.
复制标题
DOI：
10.1093/hmg/ddq040
复制
发表时间：
2010-05-01
影响因子：
3.5
通讯作者：
Skorecki K
中科院分区：
文献类型：
--
作者：
Behar DM;Rosset S;Tzur S;Selig S;Yudkovsky G;Bercovici S;Kopp JB;Winkler CA;Nelson GW;Wasser WG;Skorecki K
最近的研究确定 MYH9 是常见形式的非糖尿病终末期肾病 (ESKD) 的主要易感基因。一组包含 E-1 单倍型的非洲血统 DNA 序列变体与 ESKD 显着相关。为了确定非洲血统变异是否也与具有不同基因组背景的混合人群的疾病易感性相关，我们使用 MYH9 基因内的 42 个单核苷酸多态性 (SNP) 以及 40 个全基因组和 38 个 22 号染色体血统信息，对总共 1425 名非洲裔和西班牙裔美国人受试者（包括患有糖尿病和非糖尿病 ESKD 的透析患者和对照）进行了基因分型。标记。经过血统校正后，逻辑回归表明，在非洲裔美国人和西班牙裔美国人的新样本集中，三个 E-1 SNP 也与非糖尿病 ESKD 相关，其中与西班牙裔美国人的关联性更强。我们还发现了 MYH9 SNP，其与疾病表型的相关性比 E-1 SNP 更强。这些新关联的 SNP 可分为包含称为 S-1 的单倍型的那些，其关联在隐性或加性遗传模式下显着（rs5750248，OR 4.21，P < 0.01，西班牙裔美国人，隐性），以及包含称为 F-1 的单倍型，其关联在显性或加性遗传模式下显着（rs11912763，OR 4.59，P < 0.01）。 0.01，西班牙裔美国人，占主导地位）。这些发现强化了这样的论点，即 MYH9 的序列变异在具有不同程度的非洲血统混合的人群中很常见，并且与本文报道的相关 SNP 和单倍型存在强连锁不平衡，强烈易患非糖尿病 ESKD。
Recent studies identified MYH9 as a major susceptibility gene for common forms of non-diabetic end-stage kidney disease (ESKD). A set of African ancestry DNA sequence variants comprising the E-1 haplotype, was significantly associated with ESKD. In order to determine whether African ancestry variants are also associated with disease susceptibility in admixed populations with differing genomic backgrounds, we genotyped a total of 1425 African and Hispanic American subjects comprising dialysis patients with diabetic and non-diabetic ESKD and controls, using 42 single nucleotide polymorphisms (SNPs) within the MYH9 gene and 40 genome-wide and 38 chromosome 22 ancestry informative markers. Following ancestry correction, logistic regression demonstrated that three of the E-1 SNPs are also associated with non-diabetic ESKD in the new sample sets of both African and Hispanic Americans, with a stronger association in Hispanic Americans. We also identified MYH9 SNPs that are even more powerfully associated with the disease phenotype than the E-1 SNPs. These newly associated SNPs, could be divided into those comprising a haplotype termed S-1 whose association was significant under a recessive or additive inheritance mode (rs5750248, OR 4.21, P < 0.01, Hispanic Americans, recessive), and those comprising a haplotype termed F-1 whose association was significant under a dominant or additive inheritance mode (rs11912763, OR 4.59, P < 0.01, Hispanic Americans, dominant). These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.
登录
查看更多内容
影响因子：
30.8
作者：
Kopp, Jeffrey B.;Smith, Michael W.;Nelson, George W.;Johnson, Randall C.;Freedman, Barry I.;Bowden, Donald W.;Oleksyk, Taras;McKenzie, Louise M.;Kajiyama, Hiroshi;Ahuja, Tejinder S.;Berns, Jeffrey S.;Briggs, William;Cho, Monique E.;Dart, Richard A.;Kimmel, Paul L.;Korbet, Stephen M.;Michel, Donna M.;Mokrzycki, Michele H.;Schelling, Jeffrey R.;Simon, Eric;Trachtman, Howard;Vlahov, David;Winkler, Cheryl A.
通讯作者：
Winkler, Cheryl A.
影响因子：
19.6
作者：
Freedman, Barry I.;Hicks, Pamela J.;Bowden, Donald W.
通讯作者：
Bowden, Donald W.
影响因子：
19.6
作者：
Kopp, JB;Winkler, C
通讯作者：
Winkler, C
影响因子：
30.8
作者：
Boute, N;Gribouval, O;Antignac, C
通讯作者：
Antignac, C
影响因子：
6.1
作者：
Freedman, Barry I.;Hicks, Pamela J.;Bowden, Donald W.
通讯作者：
Bowden, Donald W.