title: Association of PDCD1 polymorphisms with childhood-onset systemic lupus erythematosus.
abstract: A regulatory single nucleotide polymorphism (SNP) PD1.3G/A located on programmed cell death 1 (PDCD1) gene, was shown to be involved in susceptibility to systemic lupus erythematosus (SLE) in Swedish, European American, and Mexican cases. However, association to childhood-onset SLE has not been analyzed. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with susceptibility to childhood-onset SLE in Mexican population. Three PDCD1 SNPs, PD1.3G/A, PD1.5C/T, PD1.6G/A, were analyzed in 250 childhood-onset SLE Mexican patients and 355 healthy controls in a case-control association study. Polymorphisms were genotyped by TaqMan technology. Stratification analysis was performed on the SLE cohort to investigate the SNP association with renal disorder. In addition, haplotypes were constructed with these three SNPs. The PD1.3A allele was significantly associated to childhood-onset SLE (P=0.0019, odds ratio (OR) 2.73, 95% confidence interval (95% CI) 1.35-5.56). The other PDCD1 SNPs did not show association. A total of 155 patients (62%) had nephritis, and no association was observed with PDCD1 SNPs. The ACG haplotype (PD1.3A, PD1.5C, PD1.6G) included almost all PD1.3A alleles, and it was more frequent in SLE patients (5.5%) than in controls (2.1%) (P=0.003; OR 2.73, 95% CI 1.37-5.46). The haplotype structure in Mexican controls was significantly different from those reported in Spanish and Swedish. Our results support association of the PD1.3A SNP to susceptibility of childhood-onset SLE in Mexican population and does not show association to lupus nephritis in this age group.
authors.affiliation: Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Velázquez-Cruz
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
authors.forename: Francisco
authors.initials: F
authors.lastname: Espinosa-Rosales
authors.forename: Roberto
authors.initials: R
authors.lastname: Carreño-Manjarrez
authors.forename: Eunice
authors.initials: E
authors.lastname: Solís-Vallejo
authors.forename: Norma D
authors.initials: ND
authors.lastname: López-Lara
authors.forename: Ivon K
authors.initials: IK
authors.lastname: Ruiz-López
authors.forename: Ana L
authors.initials: AL
authors.lastname: Rodríguez-Lozano
authors.forename: Jesús K
authors.initials: JK
authors.lastname: Estrada-Gil
authors.forename: Gerardo
authors.initials: G
authors.lastname: Jiménez-Sánchez
authors.forename: Vicente
authors.initials: V
authors.lastname: Baca
mesh_terms: D017668:Age of Onset; D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D061026:Programmed Cell Death 1 Receptor
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor