Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian Indians: Association with DRB1 *0405 and DRB1 *1001

Veena D Taneja, Marius J. Giphart, Willem Verduijn, Albert Naipal, Anand N. Malaviya, Narinder K. Mehra

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Abstract

We investigated the DRB, DQA1, and DQB1 polymorphism and haplotypes in sporadic and familial RA subjects of Asian Indian origin by PCR oligotyping using biotinylated SSOPs. Molecular subtyping of DRB1 *04 in RA patients showed strongest association with highest relative risk with DRB1 *0405, followed by DRB1 *0401. A significant decreased frequency of DRB1 *1502 was observed in patients compared to controls (X2 = 4.5). Among other alleles, DRB1 *1001 was found to be significantly increased. A total of 73.3% of patients carried the shared sequence of the third HVR (67-74) of DRB1 domain compared to its presence in only 37.6% of controls. A significant number of patients carried DR4 haplotypes on DQB1 *0302 (58%) as against DQB1 *0301 which was present only on 10.5% of the haplotypes. When compared to controls, the difference was significant for the latter allele only. Few unique DR-DQ haplotypes were observed in Asian Indians. Among DR-DQ haplotypes, DRB1 *0401-DQB1 *0302 gave the highest risk whereas DRB1 *0403-DQB1 *0301 was negatively associated. Alleles with negative charge at position 70 confer protection or are negatively associated with RA whereas among the associated alleles, glycine at position 86 resulted in higher risk than those with valine at this position. A heterogenous association of DQB1 alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB locus is not primarily associated with RA and susceptibility lies in the sequence 67-74 of the DRB1 loci.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalHuman Immunology
Volume46
Issue number1
DOIs
StatePublished - Mar 1996

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Dichlororibofuranosylbenzimidazole
Haplotypes
Rheumatoid Arthritis
Alleles
Valine
Glycine
HLA-DQA1 antigen
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian Indians : Association with DRB1 *0405 and DRB1 *1001. / Taneja, Veena D; Giphart, Marius J.; Verduijn, Willem; Naipal, Albert; Malaviya, Anand N.; Mehra, Narinder K.

In: Human Immunology, Vol. 46, No. 1, 03.1996, p. 35-41.

Research output: Contribution to journalArticle

Taneja, Veena D ; Giphart, Marius J. ; Verduijn, Willem ; Naipal, Albert ; Malaviya, Anand N. ; Mehra, Narinder K. / Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian Indians : Association with DRB1 *0405 and DRB1 *1001. In: Human Immunology. 1996 ; Vol. 46, No. 1. pp. 35-41.
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abstract = "We investigated the DRB, DQA1, and DQB1 polymorphism and haplotypes in sporadic and familial RA subjects of Asian Indian origin by PCR oligotyping using biotinylated SSOPs. Molecular subtyping of DRB1 *04 in RA patients showed strongest association with highest relative risk with DRB1 *0405, followed by DRB1 *0401. A significant decreased frequency of DRB1 *1502 was observed in patients compared to controls (X2 = 4.5). Among other alleles, DRB1 *1001 was found to be significantly increased. A total of 73.3{\%} of patients carried the shared sequence of the third HVR (67-74) of DRB1 domain compared to its presence in only 37.6{\%} of controls. A significant number of patients carried DR4 haplotypes on DQB1 *0302 (58{\%}) as against DQB1 *0301 which was present only on 10.5{\%} of the haplotypes. When compared to controls, the difference was significant for the latter allele only. Few unique DR-DQ haplotypes were observed in Asian Indians. Among DR-DQ haplotypes, DRB1 *0401-DQB1 *0302 gave the highest risk whereas DRB1 *0403-DQB1 *0301 was negatively associated. Alleles with negative charge at position 70 confer protection or are negatively associated with RA whereas among the associated alleles, glycine at position 86 resulted in higher risk than those with valine at this position. A heterogenous association of DQB1 alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB locus is not primarily associated with RA and susceptibility lies in the sequence 67-74 of the DRB1 loci.",
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T1 - Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian Indians

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AU - Taneja, Veena D

AU - Giphart, Marius J.

AU - Verduijn, Willem

AU - Naipal, Albert

AU - Malaviya, Anand N.

AU - Mehra, Narinder K.

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N2 - We investigated the DRB, DQA1, and DQB1 polymorphism and haplotypes in sporadic and familial RA subjects of Asian Indian origin by PCR oligotyping using biotinylated SSOPs. Molecular subtyping of DRB1 *04 in RA patients showed strongest association with highest relative risk with DRB1 *0405, followed by DRB1 *0401. A significant decreased frequency of DRB1 *1502 was observed in patients compared to controls (X2 = 4.5). Among other alleles, DRB1 *1001 was found to be significantly increased. A total of 73.3% of patients carried the shared sequence of the third HVR (67-74) of DRB1 domain compared to its presence in only 37.6% of controls. A significant number of patients carried DR4 haplotypes on DQB1 *0302 (58%) as against DQB1 *0301 which was present only on 10.5% of the haplotypes. When compared to controls, the difference was significant for the latter allele only. Few unique DR-DQ haplotypes were observed in Asian Indians. Among DR-DQ haplotypes, DRB1 *0401-DQB1 *0302 gave the highest risk whereas DRB1 *0403-DQB1 *0301 was negatively associated. Alleles with negative charge at position 70 confer protection or are negatively associated with RA whereas among the associated alleles, glycine at position 86 resulted in higher risk than those with valine at this position. A heterogenous association of DQB1 alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB locus is not primarily associated with RA and susceptibility lies in the sequence 67-74 of the DRB1 loci.

AB - We investigated the DRB, DQA1, and DQB1 polymorphism and haplotypes in sporadic and familial RA subjects of Asian Indian origin by PCR oligotyping using biotinylated SSOPs. Molecular subtyping of DRB1 *04 in RA patients showed strongest association with highest relative risk with DRB1 *0405, followed by DRB1 *0401. A significant decreased frequency of DRB1 *1502 was observed in patients compared to controls (X2 = 4.5). Among other alleles, DRB1 *1001 was found to be significantly increased. A total of 73.3% of patients carried the shared sequence of the third HVR (67-74) of DRB1 domain compared to its presence in only 37.6% of controls. A significant number of patients carried DR4 haplotypes on DQB1 *0302 (58%) as against DQB1 *0301 which was present only on 10.5% of the haplotypes. When compared to controls, the difference was significant for the latter allele only. Few unique DR-DQ haplotypes were observed in Asian Indians. Among DR-DQ haplotypes, DRB1 *0401-DQB1 *0302 gave the highest risk whereas DRB1 *0403-DQB1 *0301 was negatively associated. Alleles with negative charge at position 70 confer protection or are negatively associated with RA whereas among the associated alleles, glycine at position 86 resulted in higher risk than those with valine at this position. A heterogenous association of DQB1 alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB locus is not primarily associated with RA and susceptibility lies in the sequence 67-74 of the DRB1 loci.

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