Endogenous retroviral sequences represent a link between viral and genetic factors that may influence the development of systemic lupus erythematosus (SLE). The HRES‐1 human endogenous retroviral sequence is centrally located at the 1q42 chromosomal region relative to microsatellites previously associated with SLE. We therefore undertook the present study to determine the haplotypes of the HRES‐1 locus and their linkage to SLE.

One hundred six patients with SLE, 82 unrelated healthy Caucasian individuals, and 70 healthy members of 34 lupus families were examined. HRES‐1 was amplified by polymerase chain reaction (PCR) and analyzed by sequencing and restriction enzyme mapping. Microsatellites were analyzed by PCR. Haplotype construction and transmission disequilibrium testing (TDT) were performed in lupus families.

Based on 4 single‐nucleotide polymorphisms (SNPs) within a 935‐base interval, we detected 6 HRES‐1 haplotypes that were differentially segregated in unrelated Caucasian patients and control subjects (χ² = 16.86, P = 0.0048) and were in linkage disequilibrium (LD) with the D1S225 microsatellite (P = 0.0002). The microsatellites D1S225, D1S235, and D1S2785 (but not D1S229) were linked to SLE by TDT. Interestingly, LD between HRES‐1 SNPs at bases 653 and 1259 was reduced in patients with SLE (P = 0.048). The HRES‐1 653C/1259C–harboring alleles were associated with the presence of renal disease (P = 0.0021) and with the absence of lung disease (P = 0.0323), while the 956A allele was associated with the antiphospholipid syndrome in patients with SLE (P = 0.0036).

The HRES‐1 locus represents a recombination hot spot at the 1q42 chromosomal region that influences the development and disease manifestations of SLE.