rs2227631

A case-control study of 1,101 Korean individuals (612 gastric cancer patients, 489 controls) identified SERPINE1 intron 7 polymorphisms associated with diffuse-type gastric cancer (DGC) susceptibility. The SNP rs2227692 (C>T) showed significant association with DGC (OR=1.62, p=0.00084 for T-allele carriers) but not with intestinal-type gastric cancer. A risk haplotype containing rs2227692 and three additional correlated variants (c.1162+604AAAG repeat, c.1162+664_673 deletion, rs2070683) exhibited 30% higher SERPINE1 gene expression in luciferase assays (p=0.025).

This study examined variants in five genes encoding proteins in the MET receptor tyrosine kinase signaling pathway (MET, HGF, PLAUR, SERPINE1, SP1, SUB1) in 664 autism spectrum disorder (ASD) families (2,712 individuals including 1,228 with ASD) and 312 controls. Family-based association testing confirmed that the MET rs1858830 C allele was significantly associated with ASD (P=0.008), with stronger evidence in multiplex families (P=0.001), and showed a relative risk of 1.76 (95% CI: 1.19-2.62) for CC genotype. The PLAUR promoter variant rs344781 T allele also showed significant association with ASD (FBAT P=0.006, case-control P=0.007) with relative risks of 1.93-2.42, and demonstrated functional relevance through luciferase assays. Other genes in the pathway showed no significant associations.

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.