title: Genetic variants and monoallelic expression of surfactant protein-D in inflammatory bowel disease.
abstract: Surfactant protein-D (SP-D) is expressed on mucosal surfaces and functions in the innate immune response to microorganisms. We studied the genetic association of the two nonsynonymous SP-D single nucleotide polymorphisms (SNPs) rs721917 and rs2243639 in 256 inflammatory bowel disease (IBD) cases (123 CD and 133 UC) and 376 unrelated healthy individuals from an IBD population from Central Pennsylvania. Case-control analysis revealed a significant association of rs2243639 with susceptibility to Crohn's disease (CD) (p= 0.0036), but not ulcerative colitis (UC) (p= 0.883), and no association of rs721917 with CD (p= 0.328) or UC (p= 0.218). Using intestinal tissues from 19 individuals heterozygous for each SNP, we compared allelic expression of these two SNPs between diseased and matched normal tissues. rs2243639 exhibited balanced biallelic (BB) expression; while rs721917 exhibited differential allelic expression (BB 37%, imbalanced biallelic [IB] 45%, and dominant monoallelic [DM] 18%). Comparison of allelic expression pattern between diseased and matched normal tissues, 13 of 19 individuals (14 UC, 5 CD) showed a similar pattern. The six patients exhibiting a different pattern were all UC patients. The results suggest that differential allelic expression may affect penetrance of the SNP rs721917 disease-susceptibility allele in IBD. The potential impact of SP-D monoallelic expression on incomplete penetrance is discussed.
authors.affiliation: Department of Surgery, Pennsylvania State University College of Medicine, Hershey, USA. zlin@hmc.psu.edu
authors.forename: Zhenwu
authors.initials: Z
authors.lastname: Lin
authors.forename: Gerrit
authors.initials: G
authors.lastname: John
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.forename: Arthur
authors.initials: A
authors.lastname: Berg
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Kelly
authors.forename: Blaise Z
authors.initials: BZ
authors.lastname: Peterson
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Poritz
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
authors.forename: Walter A
authors.initials: WA
authors.lastname: Koltun
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D019683:Penetrance; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D