Linkage studies of hla and primary sjögren's syndrome in multicase families

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Abstract
Objective. To define the role of HLA–DR pheno‐type in the expression of primary Sjögren's syndrome (SS).Methods. A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA–A, B, and DR) were performed.Results. A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage.Conclusion. In view of the strong association with HLA‐DR3, these results suggest that the HLA‐DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non‐MHC) is discussed.