title: A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients.
abstract: The association between polymorphisms in the programmed death (PD-1) gene and susceptibility to systemic lupus erythematosus (SLE) was determined using genomic DNA, isolated from a population-based cohort of 95 SLE patients and 155 healthy controls. Polymorphisms in the complete PD-1 gene except the large intron 1 were detected by sequencing. Furthermore, the patients were stratified according to the presence or absence of lupus nephropathy. The influence of the detected single nuclear polymorphisms (SNPs) on this specific clinical disease parameter was determined. In total, we identified 12 single nucleotide polymorphisms, of which six were novel and eight were considered to be rare (the frequency of the minor allele of these was less than 1% in our study populations). We found a significant association of an intronic 6867C/G SNP in the PD-1 gene with the presence of lupus nephropathy. As the 6867C/G SNP is located in a putative binding site for the transcriptional repressor ZEB, the associated allele of this SNP potentially alters the transcriptional regulation of PD-1. This report, for the first time, indicates that a 6867C/G SNP of the PD-1 gene is associated with lupus nephropathy in Caucasian SLE patients.
authors.affiliation: Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Laustrup
authors.forename: A
authors.initials: A
authors.lastname: Voss
authors.forename: P
authors.initials: P
authors.lastname: Junker
authors.forename: S
authors.initials: S
authors.lastname: Husby
authors.forename: S T
authors.initials: ST
authors.lastname: Lillevang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D017931:DNA Primers; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology* / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D061026:Programmed Cell Death 1 Receptor; D012042:Registries; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor