HLA-linked susceptibility to rheumatoid arthritis. A study of forty-one multicase families from northern India.
OBJECTIVE
To analyze segregation of rheumatoid arthritis (RA) with HLA-DR4 and/or other alleles in multicase RA families and to compare the segregation patterns among affected and unaffected sibs.


METHODS
Forty-one multicase families (22 multiplex and 19 simplex) of northern Indian origin were studied for HLA haplotype segregation.


RESULTS
HLA haplotype sharing among affected sibs was observed more often than expected in families in which both parents were healthy (P < 0.05). RA cosegregated with a DR4 haplotype among offspring only in multiplex families in which both parents were unaffected (P < 0.05), while in simplex families, the disease segregated with DR4 only when the allele was from the affected DR4-heterozygous parent. In DR4-negative affected sib pairs, DR1, DR6, and DR10 were inherited from healthy parents more often than expected.


CONCLUSIONS
Dissimilar modes of inheritance are seen among multiplex and simplex RA families. The results of segregation analysis are compatible with the hypothesis that an epitope, rather than an individual DR antigen(s), is responsible for increased risk for development of RA.
Taneja
V
V
Histocompatibility and Immunogenetics Unit, All India Institute of Medical Sciences, New Delhi.
Mehra
N K
NK
Anand
C
C
Malaviya
A N
AN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000032:analysis
D006680:HLA Antigens; D015804:HLA-DR4 Antigen; D012217:Rheumatoid Factor