title: Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study.
abstract: BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. METHODS: Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. RESULTS: Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis.
authors.affiliation: Microbiology and Infectious Diseases, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia, 5006, Australia. annellsm@mail.wch.sa.gov.au.
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Annells
authors.forename: Prue H
authors.initials: PH
authors.lastname: Hart
authors.forename: Charles G
authors.initials: CG
authors.lastname: Mullighan
authors.forename: Susan L
authors.initials: SL
authors.lastname: Heatley
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Robinson
authors.forename: Helen M
authors.initials: HM
authors.lastname: McDonald
references.citation: Blood. 2002 May 15;99(10):3524-9
references.pmid: 11986203
references.citation: Am J Obstet Gynecol. 2002 Jul;187(1):157-63
references.pmid: 12114904
references.citation: J Biol Chem. 2002 Dec 27;277(52):50907-13
references.pmid: 12393889
references.citation: Genes Immun. 1999 Sep;1(1):3-19
references.pmid: 11197303
references.citation: Obstet Gynecol. 1990 Apr;75(4):622-6
references.pmid: 2314782
references.citation: J Reprod Immunol. 2000 Jul;47(2):185-96
references.pmid: 10924750
references.citation: Mol Immunol. 2003 Sep;40(2-4):73-84
references.pmid: 12914814
references.citation: Transplantation. 2004 Feb 27;77(4):587-96
references.pmid: 15084940
references.citation: J Immunol. 1997 Dec 15;159(12):6236-41
references.pmid: 9550427
references.citation: J Immunol. 1995 Sep 15;155(6):3013-20
references.pmid: 7673719
references.citation: Scand J Immunol. 2000 Feb;51(2):111-22
references.pmid: 10652157
references.citation: Genes Immun. 1999 Nov;1(2):137-48
references.pmid: 11196660
references.citation: Biol Reprod. 2003 Aug;69(2):718-24
references.pmid: 12700199
references.citation: Mol Immunol. 1997 Jun;34(8-9):577-82
references.pmid: 9393960
references.citation: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references.pmid: 3344216
references.citation: Obstet Gynecol. 2001 Sep;98(3):476-80
references.pmid: 11530133
references.citation: Tissue Antigens. 1997 Jul;50(1):23-31
references.pmid: 9243751
references.citation: Obstet Gynecol. 2003 Jul;102(1):162-6
references.pmid: 12850624
references.citation: Am J Obstet Gynecol. 1987 Mar;156(3):649-55
references.pmid: 3103451
references.citation: Am J Obstet Gynecol. 2004 Jan;190(1):147-51
references.pmid: 14749651
references.citation: Scand J Immunol. 1999 Feb;49(2):193-6
references.pmid: 10075024
references.citation: J Clin Endocrinol Metab. 1998 Dec;83(12):4332-7
references.pmid: 9851773
references.citation: Eur J Immunogenet. 1997 Feb;24(1):1-8
references.pmid: 9043871
references.citation: Am J Obstet Gynecol. 1989 May;160(5 Pt 1):1117-23
references.pmid: 2786341
references.citation: Am J Reprod Immunol. 1997 Mar;37(3):215-26
references.pmid: 9127642
references.citation: Infect Immun. 2000 Feb;68(2):688-93
references.pmid: 10639434
references.citation: Am J Obstet Gynecol. 2003 Jan;188(1):252-63
references.pmid: 12548226
references.citation: Infect Dis Obstet Gynecol. 2000;8(5-6):220-7
references.pmid: 11220481
references.citation: Mol Hum Reprod. 2003 Oct;9(10):625-9
references.pmid: 12970400
references.citation: Genes Immun. 2002 Feb;3(1):38-42
references.pmid: 11857060
references.citation: Hum Mol Genet. 2004 Apr 1;13(7):683-91
references.pmid: 14976157
references.citation: J Matern Fetal Neonatal Med. 2002 Jan;11(1):18-25
references.pmid: 12380603
references.citation: J Immunol Methods. 2000 Jul 31;241(1-2):33-42
references.pmid: 10915847
references.citation: Nat Rev Genet. 2001 Feb;2(2):91-9
references.pmid: 11253062
references.citation: Nucleic Acids Res. 1991 Jul 11;19(13):3561-7
references.pmid: 1852606
references.citation: Immunobiology. 2002 Sep;205(4-5):433-45
references.pmid: 12396005
references.citation: Clin Infect Dis. 2003 Sep 1;37(5):733-7
references.pmid: 12942410
references.citation: Hum Genet. 2002 Mar;110(3):207-8
references.pmid: 11935332
references.citation: Cell Signal. 2003 Nov;15(11):983-92
references.pmid: 14499341
references.citation: Mol Hum Reprod. 2002 May;8(5):447-55
references.pmid: 11994542
references.citation: Am J Obstet Gynecol. 1998 Sep;179(3 Pt 1):794-9
references.pmid: 9757992