Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis

Typeset version

 

TY  - JOUR
  - Mulcahy, B.,WaldronLynch, F.,McDermott, M. F.,Adams, C.,Amos, C. I.,Zhu, D. K.,Ward, R. H.,Clegg, D. O.,Shanahan, F.,Molloy, M. G.,OGara, F.
  - 1996
  - September
  - Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis
  - Validated
  - ()
  - 59
  - 33
  - 676
  - 683676
  - The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, cl, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF cl alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 ''shared epitope'' (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF cl and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, cl, dl, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, cl, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF cl alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 ''shared epitope'' (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF cl and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, cl, dl, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.
  - 0002-92970002-9297
  - ://WOS:A1996VN62500022://WOS:A1996VN62500022
DA  - 1996/09
ER  - 
@article{V235379946,
   = {Mulcahy,  B. and WaldronLynch,  F. and McDermott,  M. F. and Adams,  C. and Amos,  C. I. and Zhu,  D. K. and Ward,  R. H. and Clegg,  D. O. and Shanahan,  F. and Molloy,  M. G. and OGara,  F. },
   = {1996},
   = {September},
   = {Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis},
   = {Validated},
   = {()},
   = {59},
   = {33},
  pages = {676--683676},
   = {{The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, cl, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF cl alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 ''shared epitope'' (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF cl and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, cl, dl, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, cl, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF cl alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 ''shared epitope'' (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF cl and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, cl, dl, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.}},
  issn = {0002-92970002-9297},
   = {://WOS:A1996VN62500022://WOS:A1996VN62500022},
  source = {IRIS}
}
AUTHORSMulcahy, B.,WaldronLynch, F.,McDermott, M. F.,Adams, C.,Amos, C. I.,Zhu, D. K.,Ward, R. H.,Clegg, D. O.,Shanahan, F.,Molloy, M. G.,OGara, F.
YEAR1996
MONTHSeptember
JOURNAL_CODE
TITLEGenetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis
STATUSValidated
TIMES_CITED()
SEARCH_KEYWORD
VOLUME59
ISSUE33
START_PAGE676
END_PAGE683676
ABSTRACTThe major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, cl, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF cl alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 ''shared epitope'' (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF cl and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, cl, dl, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.The major histocompatibility complex class III tumor necrosis factor-lymphotoxin (TNF-LT) region (6p21.3) was investigated as a possible susceptibility locus for rheumatoid arthritis (RA). Inheritance of five TNF microsatellite markers was determined in 50 multiplex families. Overall, 47 different haplotypes were observed. One of these, the TNF a6, b5, cl, d3, e3 (H1) haplotype, was present in 35.3% of affected, but in only 20.5% of unaffected, individuals (P < .005). This haplotype accounted for 21.5% of the parental haplotypes transmitted to affected offspring and only 7.3% not transmitted to affected offspring (P = .0003). The TNF a6 and TNF cl alleles were individually associated with RA (P = .0005 and .0008, respectively), as were the HLA-DRB1 ''shared epitope'' (SE) (P = .0001) and HLA-DRB1*0401 (P = .0018). Both univariate and bivariate conditional logistic regression analysis showed significant effects of TNF cl and SE in increasing risk to RA (P < .001). Stratification by the presence of SE indicated an independent effect of the TNFc1 allele (P = .0003) and the HLA A1, B8, DR3 extended haplotype (always TNFa2, b3, cl, dl, e3) (P = .0027) in SE heterozygotes, while the H1 haplotype was associated with RA in SE homozygotes (P = .0018). The TNF-LT region appears to influence susceptibility to RA, distinct from HLA-DR.
PUBLISHER_LOCATION
ISBN_ISSN0002-92970002-9297
EDITION
URL://WOS:A1996VN62500022://WOS:A1996VN62500022
DOI_LINK
FUNDING_BODY
GRANT_DETAILS