rs1130864

This Mendelian Randomization study examined whether CRP genetic variants associated with higher blood CRP concentrations are causally related to colorectal cancer risk in 727 cases and 727 controls from the EPIC cohort. Using CRP SNPs (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) as instrumental variables, the authors found that genetically 2-fold higher CRP concentrations were associated with 74% higher colorectal cancer risk (OR 1.74, 95% CI 1.06–2.85) using the unweighted CRP-score, supporting a causal role for elevated CRP in colorectal carcinogenesis.

Case-control association study of four CRP gene polymorphisms (rs1130864, rs1205, rs1800947, rs1341665) in 651 European Caucasian systemic sclerosis patients versus 442 controls. No significant associations were found between any CRP variants and SSc susceptibility (all p-values >0.26, ORs ranging 0.88-1.11), nor in disease subphenotypes defined by specific autoantibodies (anti-centromere, anti-topoisomerase I). The study concludes CRP gene polymorphisms do not contribute to SSc genetic risk in European Caucasian populations.

This PhD thesis by Paul Henderson comprises multiple studies on paediatric inflammatory bowel disease (PIBD) in Scotland, including epidemiological studies documenting a 76% rise in IBD incidence, genetic association studies identifying ICOSLG SNP rs8126734-A as overtransmitted in IBD/CD (p=0.0467, OR 1.85 for CD; p=0.0084), CRP gene variants rs1130864-A and rs1417938-A associated with PIBD susceptibility (OR 1.56-1.89 for CD), and functional characterization of NOD2 and autophagy pathways in Crohn's disease pathogenesis.

This PhD thesis encompasses multiple studies on pediatric inflammatory bowel disease (IBD): epidemiological analysis shows rising incidence in Scotland (4.45 to 7.82 per 100,000 per year); transmission disequilibrium testing identified rs8126734-A as overtransmitted in IBD and CD (OR 1.48, p=0.047; OR 1.85 for CD, p=0.008); genome-wide association meta-analysis confirmed strong signals in ICOSLG 3'UTR for CD susceptibility; CRP gene variants (rs1417938, rs1130864) showed significant overtransmission (p=0.006, p=0.015); and faecal calprotectin demonstrated superior diagnostic accuracy for PIBD detection (sensitivity 0.93, specificity 0.74).

Population-based case-control study of 1574 colon cancer cases and 791 rectal cancer cases examining associations between CRP gene polymorphisms and colorectal cancer risk. The CRP rs1205 AA genotype was associated with increased colon cancer risk (OR 1.3, 95% CI 1.1-1.7), while rs3093075 A alleles were protective for rectal cancer (OR 0.7, 95% CI 0.5-0.9). Strongest associations were observed with specific tumor markers (KRAS2 mutations and CIMP+ phenotype), with significant interactions between CRP rs1800947 and BMI, and family history of colorectal cancer.

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.

Genome-wide association study identified five genetic loci influencing C-reactive protein (CRP) levels: rs6700896 in LEPR (-14.7% per allele, OR 1.06 for CHD), rs4537545 in IL6R (-10.8%, OR 0.94 for CHD), rs7553007 in CRP locus (-20.7%, OR 0.98 for CHD), rs1183910 in HNF1A (-13.6%), and rs4420638 in APOE-CI-CII (-21.8%, OR 1.16 for CHD). Mendelian randomization analysis of 28,112 CHD cases and 100,823 controls found no causal association between CRP genetic variants and coronary heart disease (OR 1.00, 95% CI 0.97-1.02), arguing against CRP having a causal role in atherosclerosis.

Case-control study in a Chinese population (1,046 cases, 1,035 controls) examining six CRP gene SNPs and endometrial cancer risk. While CRP SNPs alone were not significantly associated with endometrial cancer, rs1130864 and rs2794520 were found to significantly modify the association between central obesity (WHR and waist circumference) and endometrial cancer risk, with stronger effects in premenopausal women (p<0.001 for WHR).