Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III), 1991-1994.
Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III), 1991-1994.
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DOI：
10.1186/1471-2350-11-155
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发表时间：
2010-11-05
影响因子：
--
通讯作者：
Dowling NF
中科院分区：
文献类型：
--
作者：
Ned RM;Yesupriya A;Imperatore G;Smelser DT;Moonesinghe R;Chang MH;Dowling NF
蛋白尿是肾脏损害的常见标志，是肾脏疾病进展和心血管疾病发展的重要预测因素。虽然潜在的病因尚不清楚，但慢性、低级别炎症是一个可疑的关键因素。因此，参与炎症过程的基因内的遗传变异可能有助于蛋白尿的发展。我们评估了美国第三次全国健康和营养检查调查(NHANES III)第二阶段(1991-1994)参与者的27个炎症反应基因中的60个多态性。NHANES III是一项基于人群的、具有全国代表性的调查。白蛋白尿的评估指标为经对数转换后的白蛋白与肌酐的比值、≥为30 mg/g、ACR高于性别阈值。对5321名年龄在20岁或以上的参与者进行了多变量线性回归和单倍型趋势分析，以检验遗传关联。在加性和共显性遗传模型中测试了非西班牙裔白人、非西班牙裔黑人和墨西哥裔美国人之间的等位基因和基因型分布的差异。在至少一个种族/民族群体中，几个基因的变异被发现与LOG(ACR)有轻微的关联(未校正的P值和0.05)，但在粗略或完全调整的模型中，当校正错误发现率(FDR)时，没有一个是显著的。在对不同性别的蛋白尿的分析中，墨西哥裔美国人中的IL1B(Rs1143623)仍然与风险增加显著相关，而在该人群中，IL1b(Rs1143623)、C反应蛋白(Rs1800947)和NOS3(Rs2070744)与≥30 mg/g显著相关(添加模型，FDR-P<；0.05)。相比之下，在调整了多次测试后，在非西班牙裔黑人中没有发现与蛋白尿有关的变异。在非西班牙裔白人中，唯一与任何结果显著相关的变异是肿瘤坏死因子rs1800750，它未能通过该人群中Hardy-Weinberg比例的测试。在至少一个种族/民族中，MBL2、CRP、ADRB2、IL4R、NOS3和VDR的单倍型与LOG(ACR)或蛋白尿显著相关(FDR-P<；0.05)。我们的发现表明，炎症相关基因中的遗传变异对蛋白尿的易感性起到了很小的作用。还需要更多的研究来进一步评估这些未经测试的炎症基因的遗传变异是否会改变肾脏损伤的易感性。
Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria. We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR), as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models. Variants in several genes were found to be marginally associated (uncorrected P value < 0.05) with log(ACR) in at least one race/ethnic group, but none remained significant in crude or fully-adjusted models when correcting for the false-discovery rate (FDR). In analyses of sex-specific albuminuria, IL1B (rs1143623) among Mexican Americans remained significantly associated with increased odds, while IL1B (rs1143623), CRP (rs1800947) and NOS3 (rs2070744) were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P < 0.05). In contrast, no variants were found to be associated with albuminuria among non-Hispanic blacks after adjustment for multiple testing. The only variant among non-Hispanic whites significantly associated with any outcome was TNF rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within MBL2, CRP, ADRB2, IL4R, NOS3, and VDR were significantly associated (FDR-P < 0.05) with log(ACR) or albuminuria in at least one race/ethnic group. Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the susceptibility to kidney damage.
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影响因子：
19.6
作者：
Festa, A;D'Agostino, R;Haffner, SM
通讯作者：
Haffner, SM
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1093/bioinformatics/btn615
发表时间：
2009-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Carbon S;Ireland A;Mungall CJ;Shu S;Marshall B;Lewis S;AmiGO Hub;Web Presence Working Group
通讯作者：
Web Presence Working Group
影响因子：
7.7
作者：
Herrmann, SM;Ringel, J;Brand, E
通讯作者：
Brand, E
影响因子：
13.2
作者：
Coresh, J;Astor, BC;Levey, AS
通讯作者：
Levey, AS