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J Rheumatol. 2013 Jun;40(6):842-9. doi: 10.3899/jrheum.120989. Epub 2013 May 1.

Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry.

Author information

1
Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. ramosp@musc.edu

Erratum in

  • J Rheumatol. 2013 Jul;40(7):1240.

Abstract

OBJECTIVE:

Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry.

METHODS:

A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations.

RESULTS:

The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population.

CONCLUSION:

These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.

KEYWORDS:

AFRICAN AMERICANS; GENETIC ASSOCIATION STUDIES; OXYGEN COMPOUNDS; SINGLE-NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS

PMID:
23637325
PMCID:
PMC3735344
DOI:
10.3899/jrheum.120989
[Indexed for MEDLINE]
Free PMC Article

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