rs3131379

Case-control study of 673 preterm birth (PTB) cases vs 1,119 controls across four maternal cohorts testing 35 SNPs in cardiovascular, inflammatory, and metabolic disease genes. Found 13 statistically significant associations with PTB (P<0.05), more than expected by chance (binomial P=0.02). Most significant was HLA-DQA1 rs9272346 G allele protective effect in US White mothers (P=0.02, OR=0.65, 95% CI 0.46-0.94), which nominally replicated in Danish cohort (P=0.02, OR=0.85, 95% CI 0.75-0.97) but lost significance after correction for multiple testing.

Genome-wide association study of plasma beta-2 microglobulin (B2M) levels in 6,738 European Americans identified two genome-wide significant loci: the HLA region on chromosome 6 (rs9264638, p=1.8×10⁻²³) and SH2B3 on chromosome 12 (rs3184504, p=3.1×10⁻⁸). Six index SNPs in the HLA region accounted for 3.2% of log(B2M) variance and their associations were largely explained by imputed classical HLA alleles (HLA-A, HLA-B, HLA-C). The HLA locus was not associated with estimated glomerular filtration rate, while the SH2B3 locus had previously been implicated as an eGFR locus, confirming B2M as a kidney function biomarker.

Case-control study in 380 African-American SLE cases and 765 controls identified four independent SNPs in the MHC region associated with systemic lupus erythematosus. The strongest signal was rs9271366 (OR=1.70, p=5.6×10⁻⁵) near HLA-DRB1, with conditional analysis revealing three additional independent variants: rs204890 (OR=1.86, p=1.2×10⁻⁴) in ATF6B, rs2071349 (OR=1.53, p=1.0×10⁻³) in HLA-DPB1, and rs2844580 (OR=1.43, p=1.3×10⁻³) near HLA-B/MICA. A combined genotype score showed additive risk with OR=1.67 per high-risk allele (p<0.0001).

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.