POPULATION AND FAMILY STUDIES OF 3 DISEASE-RELATED POLYMORPHIC GENES IN SYSTEMIC LUPUS-ERYTHEMATOSUS

The contribution to systemic lupus erythematosus (SLE) of three lupus- associated polymorphisms (involving the C4A(2) complement component, H umhv3005 and the T cell antigen receptor alpha chain gene) are investi gated in 81 individuals from 14 multiplex SLE families, 41 unrelated l upus patients, and 88 unrelated healthy controls, The results show a s trong association between C4A deletion and SLE in these families, Whil e the current study confirms the previously reported association betwe en hv3005 deletion and sporadic SLE, the study fails to support this a ssociation in familial SLE patients, Moreover, no correlation is detec ted between the occurrence of hv3005 deletion and C4A null alleles in lupus patients, suggesting that the effects of these genetic polymorph isms on predisposition to lupus are independent. The previously report ed lupus-associated T cell receptor (TCR) alpha chain polymorphism is not detected in any of the individuals studied here, The combined data suggest that C4A null alleles predispose strongly to development of l upus, whereas the influence of hv3005 deletion is relatively weak, The results also suggest that contributions of weak susceptibility genes such as hv3005 to disease predisposition may be obscured by the effect s of stronger genetic factors and thus need to be examined in patients lacking these factors.