ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.
ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.
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DOI：
10.1016/j.ymgme.2010.08.014
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发表时间：
2010-12
影响因子：
3.8
通讯作者：
DiStefano JK
中科院分区：
文献类型：
--
作者：
Hanson RL;Millis MP;Young NJ;Kobes S;Nelson RG;Knowler WC;DiStefano JK
吞噬和细胞运动1基因ELMO 1的变异体先前与归因于2型糖尿病的肾脏疾病相关。亚利桑那州的皮马印第安人糖尿病肾病的发病率很高，这是强烈依赖于遗传因素，因此，我们试图调查ELMO 1多态性在介导这种疾病的易感性在这个人群中的作用。在一项包含257名同胞、107名糖尿病ESRD患者和108名长期糖尿病且无肾病的对照者的家族研究中，比较了141名肾病患者和416名无重度蛋白尿患者的基因型分布。我们对17.4 kb的ELMO 1进行了测序，并鉴定了19个变体。我们对12个标记物进行了基因分型，排除了与其他变异体100%基因型一致或次要等位基因频率<0.05的标记物，加上21个在早期研究中显示与ESRD相关的标记物。在家族研究中，最强有力的关联证据是与rs 1345365有关。（比值比[OR]=2.42/A等位基因拷贝[1.35-4.32]; P=0.001）和rs 10951509（OR=2.42/拷贝A等位基因[1.31-4.48]; P=0.002），两者均位于内含子13，且处于强的成对连锁不平衡（r2=0.97）。这些关联与在非裔美国人中观察到的相反，这表明糖尿病肾病与ELMO 1变异之间的关系可能涉及尚未发现的功能变体或与其他生物学变量的复杂相互作用。
Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polymorphisms in mediating susceptibility to this disease in this population. Genotype distributions were compared among 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships, and 107 cases with diabetic ESRD and 108 controls with long duration diabetes and no nephropathy. We sequenced 17.4 kb of ELMO1 and identified 19 variants. We genotyped 12 markers, excluding those in 100% genotypic concordance with other variants or with a minor allele frequency <0.05, plus 21 additional markers showing association with ESRD in earlier studies. In the family study, the strongest evidence for association was with rs1345365 (odds ratio [OR]=2.42 per copy of A allele [1.35–4.32]; P=0.001) and rs10951509 (OR=2.42 per copy of A allele [1.31–4.48]; P=0.002), both of which are located in intron 13 and are in strong pairwise linkage disequilibrium (r2=0.97). These associations were in the opposite direction from those observed in African Americans, which suggests that the relationship between diabetic kidney disease and ELMO1 variation may involve as yet undiscovered functional variants or complex interactions with other biological variables.
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影响因子：
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作者：
Ravid, M;Brosh, D;Rachmani, R
通讯作者：
Rachmani, R
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3.5
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通讯作者：
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通讯作者：
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