rs1800469

This case-control study analyzes 28 SNPs in 26 inflammatory response genes in 343 patients (100 with appendicitis, 243 controls) using TaqMan genotyping. Significant associations were found for IL-13 rs1800925 (OR=6.02, 95% CI 1.52-23.78), IL-17 rs2275913 (OR=2.38, 95% CI 1.24-4.57), and CCL22 rs223888 (OR=0.12, 95% CI 0.02-0.90), suggesting a genetic-driven inflammatory response as a pathogenic mechanism in appendicitis.

A prospective observational study of 63 breast cancer patients examining how serum biomarkers predict radiotherapy-induced cardiovascular changes. Elevated baseline TGFβ1 levels independently predict worsening global longitudinal strain and other echocardiographic abnormalities at three-year follow-up, alongside left-sided breast cancer and aromatase inhibitor use. The TGFB1 C-509T polymorphism (rs1800469) was referenced as context for understanding TGFβ1 genetic variation.

This case-control study in Japanese population evaluated CRC risk prediction models using SNPs identified in European and East Asian GWAS. An 11-SNP model combining 6 European-identified SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) with 5 East Asian-identified SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) showed significantly improved discrimination capacity compared to a 6-SNP model alone (derivation AUC 0.6392 vs 0.6125, P=0.0039; replication AUC 0.5695 vs 0.5310, P=0.0018), with cumulative risk at age 80 estimated at 13% in high-risk versus 6% in low-risk genetic groups.

Case-control study of 1,514 women (Stage I) replicated in 2,672 women (Stage II) examining 47 SNPs in 26 cytokine and cytokine receptor genes of the adaptive immune response pathway associated with breast cancer risk. The study identified differential associations by ancestry, with five SNPs showing highly significant combined effect in African American women (P-trend=0.0005), where individuals with 3+ protective genotypes had approximately 50% reduced breast cancer risk. Key associated SNPs included rs1041981, rs1800469, rs2243250, and others in immune response genes including IL4, IL4R, IL10RA, TGFB1, and IL13.

Case-control study examining 16 SNPs in four genes of the TGFβ signaling pathway (TGFB1, TGFBR1, TGFBR2, TGFBR3) and their association with HBV-related hepatocellular carcinoma in 347 Chinese HCC patients and 881 controls. rs1805110 T allele showed significant association with HCC (OR=1.21, p=0.034), with stronger effect in males (OR=1.33, p=0.005). Haplotype analysis identified protective (C-C-A-C-G, OR=0.72) and risk (T-C-A-C-G, OR=1.35) haplotypes in TGFBR3.

Candidate gene association study of 67 genetic variants in 27 inflammation and DNA repair genes with hepatitis A virus (HAV) infection susceptibility in 6,779 NHANES III participants (2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, 2,065 Mexican Americans). Among Mexican Americans, ABCB1 rs1045642 T allele was associated with lower HAV seropositivity risk (OR=0.79, p<0.001), while TGFB1 rs1800469 and XRCC1 rs1799782 T alleles were associated with increased risk (OR=1.38 and 1.57, respectively). CAT rs769214 and CYP2E1 rs2031920 showed marginal associations with decreased and increased HAV risk, respectively.

A case-control study of 160 COPD patients and 177 controls in Chinese subjects combined with a meta-analysis of 1508 COPD patients and 2608 controls found no significant association between TGFβ1 gene polymorphisms (rs1800469: OR=0.84, 95% CI 0.66-1.07; rs1982073: OR=1.06, 95% CI 0.70-1.60) and COPD risk in Asian populations, though ethnic subgroup analysis suggested possible associations in Caucasians.

A literature review summarizing epidemiologic evidence for associations between genetic polymorphisms in TGF-β signaling pathway genes and breast cancer risk and survival. The TGFB1 T+29C polymorphism (rs1982073) is the most studied variant, with meta-analysis showing a summary OR of 0.92 (95% CI=0.81-1.05) for CC genotype versus TT; results across studies were inconsistent. The TGFBR1 9A/6A polymorphism showed evidence of elevated risk with the *6A allele in some studies. For survival, TGFB1 variant C allele carriers showed reduced disease-free survival (HR=1.4, 95% CI=1.0-1.9) in one major study.

In 167 gastric cancer patients, TGFB1 +915 CG/CC genotypes were associated with poorer 2-year survival (adjusted HR 3.06, 95% CI 1.09-8.62, P=0.034) and VEGF -634 CG heterozygotes showed poorer 1-year survival (adjusted HR 2.08, 95% CI 1.03-4.22, P=0.042). No significant associations were found for overall survival with other TGFB1 polymorphisms. The study was limited by small sample size and lacked data on Helicobacter pylori infection status.

A case-parent triad study of 546 asthmatic children and their parents in Mexico City found that three TGFB1 SNPs (C-509T/rs1800469, T869C/rs1982073, and rs7258445) were significantly associated with increased asthma risk and atopy. The C-509T T allele showed RR=1.42 (95% CI 1.08-1.87) for one copy and RR=1.95 (1.36-2.78) for two copies; similar effects were found for T869C and rs7258445. The haplotype containing all three risk alleles conferred RR=1.48 (1.11-1.95) for one copy and RR=1.77 (1.22-2.57) for two copies of asthma risk.

This study demonstrates the molecular mechanism by which the TGFB1 promoter SNP c.-1347C>T (rs1800469) leads to approximately twofold differences in TGF-β1 plasma levels. Using EMSA, ChIP assays, and reporter gene constructs, the authors show that the -1347C allele exclusively recruits the AP1 transcription factor (containing JunD), which down-regulates TGFB1 expression, while the -1347T allele does not recruit AP1 and shows higher expression. The study also demonstrates HIF-1 binding to the TGFB1 promoter and competition between AP1 and HIF-1 at the -1347C site.