Fibronectin gene polymorphisms associated with fibrosing alveolitis in systemic sclerosis

被引:48
作者
Avila, JJ
Lympany, PA
Pantelidis, P
Welsh, KI
Black, CM
du Bois, RM
机构
[1] Royal Brompton Hosp, Dept Environm & Occupat Med, London SW3 6NP, England
[2] Churchill Hosp, Oxford OX3 7LJ, England
[3] Royal Free Hosp, London NW3 2QG, England
关键词
D O I
10.1165/ajrcmb.20.1.3232
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Systemic sclerosis (SSc), a multisystem immunologic disease of unknown etiology, is commonly manifested in the lung as fibrosing alveolitis (FASSc). There is evidence to support the role of genetic factors in the predisposition to pulmonary fibrosis in SSc (HLA DR3/DR52a). This association is not complete and other candidate genes are likely involved. Of these, fibronectin is a growth factor known to play a crucial role in lung fibrosis. Our study investigated whether polymorphisms of the fibronectin gene are associated with lung fibrosis in SSc. Using the polymerase chain reaction and the restriction enzymes HaeIII, MspI, HindIII, and TaqI, we assessed the restriction fragment length polymorphisms (RFLPs) in 161 patients with SSc and 253 healthy control subjects from the United Kingdom. For each restriction enzyme, three genotypes were possible corresponding to the presence of the cutting site on neither, one, or both chromosomes (HaeIII AA, AB, BE; MspI CC, CD, DD; HindIII EE, EF, FF; TaqI CGI GH, HH). There was a significant decrease of genotype BE (FASSc: 17%, control: 34%; P-corr = 0.006) with a reciprocal increase of genotype AB (FASSc: 62%, control: 46%; P-corr. = 0.022) in FASSc with the HaeIII RFLP. A significant decrease of genotype DD was observed in FASSc (FASSc: 28%, control: 41%; P-corr = 0.038) with the MspI RFLP. The coassociation of genotypes AB (HaeIII RFLP) and CD (MspI RFLP) was present in 45% of the FASSc group (P = 0.0059), with an increased relative risk of developing fibrosing alveolitis of 1.988. We conclude that genotypes of the fibronectin gene are useful prognostic factors in SSc, helping to predict individuals likely to develop pulmonary fibrosis.
引用
收藏
页码:106 / 112
页数:7
相关论文
共 32 条
  • [1] ADACHI K, 1988, AM J PATHOL, V133, P193
  • [2] BASIC LOCAL ALIGNMENT SEARCH TOOL
    ALTSCHUL, SF
    GISH, W
    MILLER, W
    MYERS, EW
    LIPMAN, DJ
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) : 403 - 410
  • [3] PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SYSTEMIC-SCLEROSIS (SCLERODERMA)
    不详
    [J]. ARTHRITIS AND RHEUMATISM, 1980, 23 (05): : 581 - 590
  • [4] ROLE OF FIBRONECTIN AS A GROWTH-FACTOR FOR FIBROBLASTS
    BITTERMAN, PB
    RENNARD, SI
    ADELBERG, S
    CRYSTAL, RG
    [J]. JOURNAL OF CELL BIOLOGY, 1983, 97 (06) : 1925 - 1932
  • [5] Black C. M., 1996, SYSTEMIC SCLEROSIS, P299
  • [6] BLACK CM, 1995, J ROY COLL PHYS LOND, V29, P119
  • [7] TRANSFORMING GROWTH-FACTOR-BETA REGULATES THE SPLICING PATTERN OF FIBRONECTIN MESSENGER-RNA PRECURSOR
    BORSI, L
    CASTELLANI, P
    RISSO, AM
    LEPRINI, A
    ZARDI, L
    [J]. FEBS LETTERS, 1990, 261 (01) : 175 - 178
  • [8] IMMUNOGENETIC PREDICTION OF PULMONARY FIBROSIS IN SYSTEMIC-SCLEROSIS
    BRIGGS, DC
    VAUGHAN, RW
    WELSH, KI
    MYERS, A
    DUBOIS, RM
    BLACK, CM
    [J]. LANCET, 1991, 338 (8768) : 661 - 662
  • [9] A FREQUENT HINDIII RFLP OF THE HUMAN FIBRONECTIN GENE (FN1)
    COLOMBI, M
    GARDELLA, R
    BARLATI, S
    [J]. NUCLEIC ACIDS RESEARCH, 1988, 16 (18) : 9074 - 9074
  • [10] A FREQUENT HAEIII RFLP OF THE HUMAN FIBRONECTIN GENE
    COLOMBI, M
    GARDELLA, R
    BARLATI, S
    VAHERI, A
    [J]. NUCLEIC ACIDS RESEARCH, 1987, 15 (16) : 6761 - 6761