rs103294

This case-control association study demonstrates that functional LILRA3 (leukocyte immunoglobulin-like receptor A3) is a novel genetic risk factor for adult-onset Still's disease (AOSD) in Chinese populations. The LILRA3 6.7-kb deletion polymorphism showed significant association with AOSD (OR 2.089 [95% CI 1.030-4.291], P = 0.034), and its tagging SNP rs103294 was also significantly associated (OR 2.179 [95% CI 1.040-4.650], P = 0.047). Functional LILRA3 was correlated with enhanced neutrophil activation and NET formation, suggesting a pathogenic role in AOSD pathogenesis.

This case-control study in Han Chinese populations (1,618 Northern Han cases/controls + 575 Southern Han cases/controls) identified functional LILRA3 (non-deleted allele) as a novel genetic risk factor for rheumatoid arthritis, particularly ACPA-positive RA and in males (OR 4.47, P=1.09×10⁻⁶ in males; OR 1.75, P=3.05×10⁻⁴ for ACPA+ RA). The tagging SNP rs103294 showed similar associations (meta-analysis P=5.63×10⁻⁶, OR 1.83). Functional LILRA3 was associated with increased joint destruction in early ACPA-positive RA and higher LILRA3 mRNA expression.

Genome-wide association study of 474 prostate cancer cases and 458 controls from West African men identified a novel prostate cancer susceptibility locus at 10p14 marked by rs7918885 (p=1.29×10⁻⁷), localized to an intron of the lncRNA gene RP11-543F8.2. A stratified analysis by Gleason score revealed additional associations including rs34575154 in PCDHA1 at 5q31.3 (p=3.66×10⁻⁸) for high-grade disease and rs985081 at Xq28 (p=8.66×10⁻⁹) for low-grade disease. Validation in the African Ancestry Prostate Cancer GWAS Consortium showed limited replication, with only rs2993385 at 10p14 reaching nominal significance (p<0.05), highlighting population-specific genetic architecture.

Systematic literature review of 22 GWAS studies identifying 53 SNPs in 29 genomic loci associated with aggressive and progressive prostate cancer, particularly in low-grade disease. Functional analysis of 21 SNPs revealed involvement in the MYC/POU5F1B pathway (rs1447295, rs6983267, rs4242382), androgen receptor pathway (rs17021918, rs10486567, rs7679673, rs2939244), and PSA/KLK3 biomarkers (rs2735839, rs10993994). SNPs were integrated with somatic copy number aberration data, with 17 SNPs found in regions of recurrent CNAs predictive of progression; notably, rs1447295 and 7 other SNPs cluster in 8q24 gain regions harboring MYC.

This systematic review identified 53 unique SNPs in 29 genomic loci associated with aggressive prostate cancer progression and poor outcomes from GWAS studies. Functional studies implicated 21 SNPs as modulating the androgen receptor pathway, MYC oncogene, and PSA-related genes, with rs1447295 and rs10993994 being replicated across multiple populations and associated with unfavorable pathological features in low-grade prostate cancer.