The differential effect of genetic variation on soluble CD14 levels in human plasma and milk

被引:24
作者
Guerra, S
Lohman, IC
LeVan, TD
Wright, AL
Martinez, FD
Halonen, M
机构
[1] Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ 85724 USA
[2] Univ Arizona, Coll Med, Dept Med, Tucson, AZ 85724 USA
[3] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ 85724 USA
[4] Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA
[5] Univ Arizona, Coll Publ Hlth, Tucson, AZ USA
关键词
CD14; antigen; gene regulation; human milk; lipopolysaccharide; pregnancy; single nucleotide polymorphism;
D O I
10.1111/j.1600-0897.2004.00207.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
PROBLEM: The protein CD14 is a pattern recognition receptor for bacterial lipopolysaccharide (LPS). Whether genetic variation has the same influence on soluble CD14 (sCD14) levels in human plasma and milk remains to be determined. METHOD OF STUDY: We measured sCD14 levels in plasma during pregnancy (n = 196) and in milk in the postpartum (n = 152) for women genotyped for the single nucleotide polymorphisms (SNPs) at positions -1619, -550, and -159 from the transcription start site of the CD14 gene. RESULTS: Plasma- and milk-sCD14 levels differed significantly both by CD14/-1619 and CD14/-550 genotypes and by haplotypes. Most interestingly, sCD14 levels were regulated differentially by the same genetic variants in plasma and milk, with the CD14/-550T allele and the corresponding are ATC haplotype associated with high sCD14 in milk but low sCD14 in plasma. A correlation between sCD14 levels in plasma and milk was absent (r = 0.091, P = NS). CONCLUSIONS: Our findings suggest the existence of cell-specific regulation mechanisms of CD14 gene expression.
引用
收藏
页码:204 / 211
页数:8
相关论文
共 35 条
[21]   A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity [J].
LeVan, TD ;
Bloom, JW ;
Bailey, TJ ;
Karp, CL ;
Halonen, M ;
Martinez, FD ;
Vercelli, D .
JOURNAL OF IMMUNOLOGY, 2001, 167 (10) :5838-5844
[22]   Elevated levels of serum-soluble CD14 in human immunodeficiency virus type 1 (HIV-1) infection:: Correlation to disease progression and clinical events [J].
Lien, E ;
Aukrust, P ;
Sundan, A ;
Müller, F ;
Froland, SS ;
Espevik, T .
BLOOD, 1998, 92 (06) :2084-2092
[23]  
Martinez FD, 1999, LANCET, V354, pS12, DOI 10.1016/S0140-6736(99)90437-3
[24]   Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis [J].
Nockher, WA ;
Wick, M ;
Pfister, HW .
JOURNAL OF NEUROIMMUNOLOGY, 1999, 101 (02) :161-169
[25]   CD14 IS A PATTERN-RECOGNITION RECEPTOR [J].
PUGIN, J ;
HEUMANN, D ;
TOMASZ, A ;
KRAVCHENKO, VV ;
AKAMATSU, Y ;
NISHIJIMA, M ;
GLAUSER, MP ;
TOBIAS, PS ;
ULEVITCH, RJ .
IMMUNITY, 1994, 1 (06) :509-516
[26]  
Schneider S., 2000, ARLEQUIN VER 2000 SO
[27]   Common polymorphism in the promoter of the CD14 monocyte receptor gene is associated with acute myocardial infarction in Japanese men [J].
Shimada, K ;
Watanabe, Y ;
Mokuno, H ;
Iwama, Y ;
Daida, H ;
Yamaguchi, H .
AMERICAN JOURNAL OF CARDIOLOGY, 2000, 86 (06) :682-+
[28]   Testing for linkage disequilibrium in genotypic data using the expectation-maximization algorithm [J].
Slatkin, M ;
Excoffier, L .
HEREDITY, 1996, 76 :377-383
[29]   A new statistical method for haplotype reconstruction from population data [J].
Stephens, M ;
Smith, NJ ;
Donnelly, P .
AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (04) :978-989
[30]   CD14 expression and production by human hepatocytes [J].
Su, GL ;
Dorko, K ;
Strom, SC ;
Nüssler, AK ;
Wang, SC .
JOURNAL OF HEPATOLOGY, 1999, 31 (03) :435-442