rs2010963

This systematic review analyzed 24 studies examining 31 genes and 62 genetic variants associated with anterior cruciate ligament rupture (ACLR). Key findings show mixed evidence for collagen variants: COL1A1 rs1800012 showed protective association in European ancestry populations (OR=2.8, p=0.040), while COL1A2 rs42524 and rs2621215 conferred increased risk (OR=5.73 and 4.29 respectively). VEGFA polymorphisms rs2010963 and rs699947 showed conflicting associations across studies, and most major variants in IL6, IL1B, MMP genes, and inflammatory markers showed no consistent associations with ACLR across populations, highlighting the need for gender and ancestry-stratified analyses.

A comprehensive meta-analysis of 50 case-control studies from the Indian subcontinent identified genetic variants modifying lung cancer risk, finding FDR-corrected associations for rs3547/XRCC1 (OR=1.83-2.72) and rs1048943/CYP1A1 (OR=2.07). The rs1048943/CYP1A1 variant showed strongest associations with adenocarcinoma (OR=3.38) and squamous cell carcinoma (OR=3.53) with significant effect modification by smoking status. Global meta-analysis confirmed rs1048943/CYP1A1 association across world populations (OR=1.22, p=0.01).

This Iranian cohort study investigated the association between VEGF rs2010963 (+405 C/G) polymorphism and coronary artery disease (CAD) in 520 subjects (347 CAD patients, 173 controls). The C allele was significantly associated with increased CAD risk (OR=3.43-3.65) and was linked to reduced 5-year cardiovascular survival (92.3% for C allele vs 94.3% for G allele in CAD patients). The polymorphism was not associated with CAD severity but showed elevated hazard ratios for CAD-related mortality (HR 1.73 for C allele, p=.056).

This retrospective cohort study of 121 metastatic renal cell carcinoma (mRCC) patients treated with sunitinib evaluated 10 SNPs in angiogenesis-related genes (VEGFA, VEGFR1, VEGFR2, VEGFR3) as prognostic markers. Kaplan-Meier and Cox regression analyses identified rs9582036 in VEGFR1 (AA/AC genotypes vs CC wild-type) as significantly associated with improved overall survival (HR=0.241, p=0.018), while rs699947 in VEGFA showed associations with progression-free survival. No significant associations were found between SNPs and sunitinib-induced adverse effects (hand-foot syndrome, hypertension) after multiple testing correction.

Case-control study of 277 Chinese CHD patients and 293 controls examining 29 SNPs in NFATC1 signaling pathway genes (NFATC1, VEGFR, VEGF, RANKL, FGFR1, BCL-6, ZNRD1). After Bonferroni correction, rs4531631 (RANKL) showed significant association with increased CHD risk (homozygous AA vs. GG: OR 2.38, p=0.001; recessive: OR 2.54, p=0.0003), as did rs13317 (FGFR1) (recessive CC vs. CT/TT: OR 2.06, p=0.00196). Authors suggest these variants may be potential biomarkers for genetic diagnosis and treatment of CHD.

This PhD thesis investigated pharmacogenetics of microRNAs and immune system genes in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy. In 265 LARC patients, five SNPs were identified as predictive biomarkers of pathological response: DROSHA-rs10719 (OR=1.87, p=0.0274) and SMAD3-rs17228212 (OR=2.01, p=0.0049) were unfavorable, while SMAD3-rs744910 (OR=0.45, p=0.0153), SMAD3-rs745103 (OR=0.48, p=0.0471), and TRBP-rs6088619 (OR=0.39, p=0.0125) were protective. In 235 LARC patients, three prognostic biomarkers for 2-year disease-free survival were identified: IL17F-rs641701 (HR=3.23, p=0.003), IL17F-rs9463772 (HR=2.89, p=0.002), and STAT3-rs8069645 (HR=0.50, p=0.044).

A case-control study of 79 Brazilian women with pre-eclampsia/eclampsia and 210 controls investigated genetic polymorphisms in VEGF (G-634C) and IL1A (rs3783550). No significant association was found for VEGF G-634C with pre-eclampsia. However, the IL1A rs3783550 polymorphism showed significant association (p=0.0278), with the AA genotype more frequent in pre-eclamptic women and the C allele protective (OR=0.271, 95% CI 0.096-0.762, p=0.013).

This pharmacogenetic study examined how VEGFA gene polymorphisms affect antihypertensive responses to enalapril in 102 hypertensive patients. The g.-2578C>A (rs699947) AA genotype and AGG haplotype were associated with greater blood pressure reduction (20-22 mmHg greater mean BP decrease at 20 mg/day dose), while the CC genotype and CGG haplotype showed blunted responses. The findings suggest VEGFA polymorphisms modulate ACE inhibitor efficacy through effects on VEGF expression and vasodilation.

This candidate gene association study of 370 CCA cases and 740 controls identified initial associations between COX-2 variants rs2143417 (OR=1.52) and rs689466 (OR=1.36) and cholangiocarcinoma risk; however, these findings failed replication in an independent cohort of 212 cases and 424 controls (rs2143417 OR=1.04, rs689466 OR=1.08). No SNP variants showed significant associations with CCA survival, and NKG2D variants previously reported to be associated with CCA did not replicate.

This study evaluated 835 neovascular age-related macular degeneration (nAMD) patients from the CATT trial for associations between 8 SNPs in the VEGF signaling pathway (7 in VEGF-A: rs699946, rs699947, rs833069, rs833070, rs1413711, rs2010963, rs2146323; 1 in VEGFR-2: rs2071559) and response to anti-VEGF therapy with ranibizumab or bevacizumab. While four VEGF-A SNPs showed nominal associations with retinal thickness (p=0.03-0.04 and p=0.006), adjusted p-values were not statistically significant (p=0.24-0.45). The study found no pharmacogenetic associations between these VEGF pathway SNPs and visual acuity, anatomical outcomes, or injection frequency, concluding that these variants do not substantially influence response to anti-VEGF therapy.

A case-control study of 1555 colon and 754 rectal cancer cases examined genetic variation in VEGFA, FLT1, and KDR genes. FLT1 was significantly associated with colon cancer risk (P_ARTP=0.045) and VEGFA with rectal cancer (P_ARTP=0.036). Multiple SNPs were associated with tumor molecular phenotypes (CIMP+, MSI+, TP53 mutations), and aspirin/NSAID use, smoking, and BMI modified these associations.

PhD dissertation examining genetic variants in collagen genes (COL22A1, COL27A1, COL11A1) and anterior cruciate ligament injury risk in Polish athletes. Paper 1 is a systematic review of genetic determinants of ACL rupture. Papers 2 and 3 are case-control association studies finding no significant associations between SNPs rs11784270/rs6577958 (COL22A1), rs946053 (COL27A1), and rs3753841 (COL11A1) and non-contact ACL injury risk in Polish athletes.

Two-stage replication study of 9 SNPs in 8 genes previously associated with breast cancer survival in 6,307 Chinese women (Stage 1: 1,115 cases, Stage 2: 5,192 cases). MMP7 rs11225297 and MMP8 rs11225395 showed consistent associations with overall survival, with rare alleles conferring 20-40% improved survival (HR 0.4-0.6 and 0.6 for TT genotypes respectively, p<0.001).

Case-control study of 766 glioma patients and 824 controls from a Chinese population investigating associations between 9 VEGFA gene polymorphisms and glioma risk. Three SNPs showed suggestive associations: rs2010963 (OR=1.29, 95% CI 1.04-1.58), rs3025030 (OR=2.21, 95% CI 1.18-4.14), and rs3024994 (protective, OR=0.66, 95% CI 0.47-0.94). A notable cumulative effect was observed with each additional adverse genotype increasing glioma risk 1.38-fold (p=8.4×10⁻⁵).

Comprehensive review evaluating SNPs as genetic predictors of choroidal neovascularization (CNV) response to photodynamic therapy with verteporfin (PDT-V). The paper examines pharmacogenetic correlations for thrombo-coagulative pathway variants (MTHFR rs1801133, F5 rs6025, F2 rs1799963, F13A1 rs5985), complement/inflammatory variants (CFH, HTRA1, CRP, ARMS2), and VEGFA variants (rs699947, rs2146323), concluding that specific SNPs show clinical plausibility as markers to optimize PDT-V efficacy and guide therapeutic approaches in neovascular macular degeneration.

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.

This case-control study of 1,423 Russian athletes and 1,132 controls examined 15 metabolic gene polymorphisms associated with elite endurance athlete status. Ten 'endurance alleles' were identified: rs4253778 (PPARA), rs2016520 (PPARD), rs8192678 (PPARGC1A), rs7732671 (PPARGC1B), rs1937 (TFAM), rs660339 (UCP2), rs1800849 (UCP3), rs2010963 (VEGFA), NFATC4 rs2229309, and PPP3R1 promoter 5I. The proportion of subjects with ≥9 endurance alleles was significantly higher in elite endurance athletes versus controls (85.7% vs 37.8%, P=7.6×10⁻⁶). The number of endurance alleles positively correlated with slow-twitch muscle fiber proportion (r=0.50, P=4.0×10⁻⁴) and maximal oxygen consumption (r=0.46, P=7.0×10⁻⁴).

Meta-analysis of 27 case-control studies (5,175 IMID patients, 7,069 controls) examining VEGF +405G>C polymorphism (rs2010963) and immune-mediated inflammatory diseases. No overall association was found; however, ethnicity-stratified analysis revealed the +405C allele was protective in Asians (OR 0.90, p=0.031) but a risk factor in Caucasians (OR 1.15, p=0.012).