Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster.
A dense gene-based SNP map was constructed across a 360-kb region containing the interleukin-1 gene cluster (IL1A, IL1B, and IL1RN), focusing on IL1RN. In total, 95 polymorphisms were confirmed or identified primarily by direct sequencing. Polymorphisms were precisely mapped to completed BAC and genomic sequences spanning this region. The polymorphisms were typed in 443 case-control subjects from Caucasian and African American groups. Consecutive pair-wise marker linkage disequilibrium was not strictly correlated with distance and ranged from D'=0.0079 to 1.000 and D'=0.0521 to 1.0000 in Caucasians and African Americans, respectively. Single markers and haplotypes in IL1 cluster genes were evaluated for association with end-stage renal disease (ESRD). Eleven SNPs show some evidence of association with ESRD, with the strongest associations in two IL1A variants, one SNP, rs1516792-3, in intron 5 (p=0.0015) and a 4-bp insertion/deletion within the 3'UTR, rs16347-2 (p=0.0024), among African Americans with non-T2DM-associated ESRD.
Bensen
Jeannette T
JT
The Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. jbensen@wfubmc.edu
Langefeld
Carl D
CD
Hawkins
Gregory A
GA
Green
Linda E
LE
Mychaleckyj
Josyf C
JC
Brewer
Catherine S
CS
Kiger
Deborah S
DS
Binford
Scott M
SM
Colicigno
Carla J
CJ
Allred
Dax C
DC
Freedman
Barry I
BI
Bowden
Donald W
DW
D001741:Black or African American; D017931:DNA Primers; D004586:Electrophoresis; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People
D017931:DNA Primers; D007375:Interleukin-1