Endothelial nitric oxide synthase gene polymorphism is associated with systemic lupus erythematosus

Norma C. Serrano, Carolina Páez, Paula A. Correa, Juan Manuel Anaya

Resultado de la investigación: Contribución a RevistaArtículo

29 Citas (Scopus)

Resumen

Objective. In systemic lupus erythematosus (SLE), endothelial nitric oxide synthase (eNOS) gene locus has been found to be suggestive of linkage with disease, nitric oxide (NO) is produced in significant amounts, and endothelial cell dysfunction is observed. eNOS gene polymorphism may affect both the synthesis of eNOS protein and its enzymatic activity. We examined the influence of eNOS gene polymorphisms on susceptibility to SLE. Methods. Genomic DNA from 88 Northwestern Colombian women with SLE, as well as 199 controls matched for sex, age, and ethnicity, was genotyped for the -786T→C polymorphism in the promoter region, the intron 4 variable number of tandem repeats, and the Glu298Asp polymorphism in exon 7 of the eNOS gene by polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and allele frequency comparisons, a Hardy-Weinberg equilibrium test, and linkage disequilibrium (LD) analysis were performed. Results. The intron 4b allele was associated with SLE (OR 2.2, 95% CI 1.29-3.60, pc = 0.005) as was the 4bb genotype (OR 2.9, 95% CI 1.61-5.33, pc = 0.0009), while the 4a allele was protective (OR 0.4, 95% CI 0.26-0.76, pc = 0.005), as was the 4ab genotype (OR 0.29, 95% CI 0.15-0.56, pc <0.0001). In controls, all loci were in linkage disequilibrium (p <0.02). In patients, intron 4 was in Hardy-Weinberg disequilibrium, due to an excess of homozygotes (p = 0.01). Conclusion. eNOS polymorphism influences SLE predisposition. Since intron 4bb genotype is responsible for higher levels of eNOS synthesis and intron 4 ab genotype is associated with lower synthesis, our results might provide insight into the elevated levels of NO observed in SLE patients.
Idioma originalEnglish (US)
Páginas (desde-hasta)2163-2168
Número de páginas6
PublicaciónJournal of Rheumatology
EstadoPublished - nov 1 2004

Huella dactilar

Nitric Oxide Synthase Type III
Systemic Lupus Erythematosus
Introns
Genes
Genotype
Linkage Disequilibrium
Nitric Oxide
Alleles
Minisatellite Repeats
Internal-External Control
Homozygote
Genetic Promoter Regions
Gene Frequency
Restriction Fragment Length Polymorphisms
Haplotypes
Exons
Endothelial Cells
Polymerase Chain Reaction
DNA
Proteins

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title = "Endothelial nitric oxide synthase gene polymorphism is associated with systemic lupus erythematosus",
abstract = "Objective. In systemic lupus erythematosus (SLE), endothelial nitric oxide synthase (eNOS) gene locus has been found to be suggestive of linkage with disease, nitric oxide (NO) is produced in significant amounts, and endothelial cell dysfunction is observed. eNOS gene polymorphism may affect both the synthesis of eNOS protein and its enzymatic activity. We examined the influence of eNOS gene polymorphisms on susceptibility to SLE. Methods. Genomic DNA from 88 Northwestern Colombian women with SLE, as well as 199 controls matched for sex, age, and ethnicity, was genotyped for the -786T→C polymorphism in the promoter region, the intron 4 variable number of tandem repeats, and the Glu298Asp polymorphism in exon 7 of the eNOS gene by polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and allele frequency comparisons, a Hardy-Weinberg equilibrium test, and linkage disequilibrium (LD) analysis were performed. Results. The intron 4b allele was associated with SLE (OR 2.2, 95{\%} CI 1.29-3.60, pc = 0.005) as was the 4bb genotype (OR 2.9, 95{\%} CI 1.61-5.33, pc = 0.0009), while the 4a allele was protective (OR 0.4, 95{\%} CI 0.26-0.76, pc = 0.005), as was the 4ab genotype (OR 0.29, 95{\%} CI 0.15-0.56, pc <0.0001). In controls, all loci were in linkage disequilibrium (p <0.02). In patients, intron 4 was in Hardy-Weinberg disequilibrium, due to an excess of homozygotes (p = 0.01). Conclusion. eNOS polymorphism influences SLE predisposition. Since intron 4bb genotype is responsible for higher levels of eNOS synthesis and intron 4 ab genotype is associated with lower synthesis, our results might provide insight into the elevated levels of NO observed in SLE patients.",
author = "Serrano, {Norma C.} and Carolina P{\'a}ez and Correa, {Paula A.} and Anaya, {Juan Manuel}",
year = "2004",
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language = "English (US)",
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Endothelial nitric oxide synthase gene polymorphism is associated with systemic lupus erythematosus. / Serrano, Norma C.; Páez, Carolina; Correa, Paula A.; Anaya, Juan Manuel.

En: Journal of Rheumatology, 01.11.2004, p. 2163-2168.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Endothelial nitric oxide synthase gene polymorphism is associated with systemic lupus erythematosus

AU - Serrano, Norma C.

AU - Páez, Carolina

AU - Correa, Paula A.

AU - Anaya, Juan Manuel

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Objective. In systemic lupus erythematosus (SLE), endothelial nitric oxide synthase (eNOS) gene locus has been found to be suggestive of linkage with disease, nitric oxide (NO) is produced in significant amounts, and endothelial cell dysfunction is observed. eNOS gene polymorphism may affect both the synthesis of eNOS protein and its enzymatic activity. We examined the influence of eNOS gene polymorphisms on susceptibility to SLE. Methods. Genomic DNA from 88 Northwestern Colombian women with SLE, as well as 199 controls matched for sex, age, and ethnicity, was genotyped for the -786T→C polymorphism in the promoter region, the intron 4 variable number of tandem repeats, and the Glu298Asp polymorphism in exon 7 of the eNOS gene by polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and allele frequency comparisons, a Hardy-Weinberg equilibrium test, and linkage disequilibrium (LD) analysis were performed. Results. The intron 4b allele was associated with SLE (OR 2.2, 95% CI 1.29-3.60, pc = 0.005) as was the 4bb genotype (OR 2.9, 95% CI 1.61-5.33, pc = 0.0009), while the 4a allele was protective (OR 0.4, 95% CI 0.26-0.76, pc = 0.005), as was the 4ab genotype (OR 0.29, 95% CI 0.15-0.56, pc <0.0001). In controls, all loci were in linkage disequilibrium (p <0.02). In patients, intron 4 was in Hardy-Weinberg disequilibrium, due to an excess of homozygotes (p = 0.01). Conclusion. eNOS polymorphism influences SLE predisposition. Since intron 4bb genotype is responsible for higher levels of eNOS synthesis and intron 4 ab genotype is associated with lower synthesis, our results might provide insight into the elevated levels of NO observed in SLE patients.

AB - Objective. In systemic lupus erythematosus (SLE), endothelial nitric oxide synthase (eNOS) gene locus has been found to be suggestive of linkage with disease, nitric oxide (NO) is produced in significant amounts, and endothelial cell dysfunction is observed. eNOS gene polymorphism may affect both the synthesis of eNOS protein and its enzymatic activity. We examined the influence of eNOS gene polymorphisms on susceptibility to SLE. Methods. Genomic DNA from 88 Northwestern Colombian women with SLE, as well as 199 controls matched for sex, age, and ethnicity, was genotyped for the -786T→C polymorphism in the promoter region, the intron 4 variable number of tandem repeats, and the Glu298Asp polymorphism in exon 7 of the eNOS gene by polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and allele frequency comparisons, a Hardy-Weinberg equilibrium test, and linkage disequilibrium (LD) analysis were performed. Results. The intron 4b allele was associated with SLE (OR 2.2, 95% CI 1.29-3.60, pc = 0.005) as was the 4bb genotype (OR 2.9, 95% CI 1.61-5.33, pc = 0.0009), while the 4a allele was protective (OR 0.4, 95% CI 0.26-0.76, pc = 0.005), as was the 4ab genotype (OR 0.29, 95% CI 0.15-0.56, pc <0.0001). In controls, all loci were in linkage disequilibrium (p <0.02). In patients, intron 4 was in Hardy-Weinberg disequilibrium, due to an excess of homozygotes (p = 0.01). Conclusion. eNOS polymorphism influences SLE predisposition. Since intron 4bb genotype is responsible for higher levels of eNOS synthesis and intron 4 ab genotype is associated with lower synthesis, our results might provide insight into the elevated levels of NO observed in SLE patients.

M3 - Article

SP - 2163

EP - 2168

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

ER -