rs1800947

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.

Case-control study nested in the Physicians' Health Study examining four CRP gene SNPs (rs3093075, rs2808630, rs1800947, rs1417938) and prostate cancer risk among 1,286 cases and 1,264 controls. No SNPs were significantly associated with overall prostate cancer risk. However, rs1800947 may be associated with higher-grade disease (OR 1.5, 95% CI 0.9-1.7), and SNPs rs3093075, rs1800947, and rs1417938 were significantly associated with altered plasma CRP levels.

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).

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.

This study examined associations between CRP gene haplotypes and dispositional optimism in 1,084 elderly Dutch subjects using a Mendelian randomization design. Six CRP polymorphisms (rs2808628, rs2808630, rs1205, rs1800947, rs1417938, rs3091244) were genotyped and CRP haplotypes were found to determine plasma CRP levels (adjusted β=0.094, p<0.001). However, CRP haplotypes were associated with dispositional optimism only in obese subjects (adjusted β=-0.068, p=0.03), suggesting obesity modulates the relationship between genetic CRP elevation and optimism.

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.

Nested case-control study of 258 prostate cancer cases and 258 matched controls in the CLUE II prospective cohort examining genetic variants in inflammation and obesity-related genes. The IL10 -1082G>A variant (rs1800896, A allele) was positively associated with prostate cancer risk (AG vs GG: OR=1.69, 95% CI 1.10-2.60; AA vs GG: OR=1.81, 95% CI 1.11-2.96), while a TLR4 variant (rs4986790) showed inverse association, and no consistent associations were found for obesity-related gene variants.

Fine-mapping study of C-reactive protein (CRP) regulation in 594 African Americans using dense SNP genotyping and Bayesian model selection. Found rs3091244(T) allele as the key functional variant regulating CRP expression with additive effects (Bayes factor >100), explaining 5.20% of CRP variance with β=0.312 (95% CI 0.146-0.491). Secondary analysis supported a two-SNP model including rs12728740, which segregated with European-origin haplotypes. The study demonstrates that weaker linkage disequilibrium in African Americans resolved genetic ambiguity seen in European populations.

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).

This study re-sequenced ~1,000 chromosomes of the CRP gene across diverse populations (European-American, African-American, Asian, Mexican, and Indo-Pakistani) to catalog both common and rare genetic variation. The authors identified 40 SNPs total, including three with rsIDs (rs3091244, rs1800947, rs3093058), and discovered novel nonsynonymous variants such as Pro133Lys (site 2513), Tyr67His (site 2314), and Gly166Glu (site 2612). When the novel nonsynonymous variants were genotyped in 7,296 individuals from NHANES III, they were found to be extremely rare, with minor allele frequencies below 1%, suggesting that while deep re-sequencing identifies potentially damaging coding variants, most occur at frequencies too low to study in large population surveys.