BioMed Central | Full text | 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
Renée M Ned1 , Ajay Yesupriya1 , Giuseppina Imperatore2 , Diane T Smelser1,3 , Ramal Moonesinghe4 , Man-huei Chang1 and Nicole F Dowling1

1 Office of Public Health Genomics, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA

2 Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA

3 American Society of Human Genetics Fellow, Centers for Disease Control and Prevention, Atlanta, GA, USA

4 Office of Minority Health and Health Disparities, Office of the Director, Centers for Disease Control and Prevention, Atlanta, GA, USA

BMC Medical Genetics 2010, 11:155doi:10.1186/1471-2350-11-155

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2350/11/155

Received: 15 April 2010
Accepted: 5 November 2010
Published: 5 November 2010

© 2010 Ned et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background
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.

Methods
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.

Results
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. Conclusions 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. full-text: BioMed Central | Full text | 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