rs1799964

This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.

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.

Genetic dissection of acute anterior uveitis (AAU) using high-density Immunochip genotyping in 1,711 AAU cases and 10,000 controls identifies HLA-B27 tag SNP rs116488202 (OR=16.8, P<1×10⁻³⁰⁰) as the strongest association, and three genome-wide significant non-MHC loci (IL23R, chromosome 2p15 intergenic region, and ERAP1) shared with ankylosing spondylitis. Five additional suggestive loci including IL10-IL19, IL18R1-IL1R1, IL6R, KIF21B, and EYS are identified, with shared genetic pathways with inflammatory bowel disease suggesting common etiologic mechanisms.

Population-based case-control study of 876 cervical cancer cases, 517 vulvar cancer cases, and 1,100 controls examining genetic variation in TLR and NFκB pathways. The TNF region was significantly associated with cervical cancer (gene-based P=2.0×10⁻⁴) and vulvar cancer (gene-based P=1.0×10⁻⁴) risk. The rare A allele of rs2239704 in the LTA gene 5' UTR was significantly associated with increased cervical cancer risk (OR=1.31, 95% CI: 1.15–1.50) and vulvar cancer risk (OR=1.51, 95% CI: 1.30–1.75).

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.

This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.

First study evaluating the pharmacogenetic role of rs1143634 IL1B polymorphism and TNF promoter polymorphisms in infliximab-treated inflammatory bowel disease patients. Found rs1143634 C allele associated with higher serum IL1β concentrations (p=0.0345) and lower response to infliximab in Crohn's disease (p=0.027 for clinical remission). No significant associations found with TNF polymorphisms.

Genetic association study of 202 melanoma patients examining SNPs in 24 candidate genes related to pigmentation and wound healing in relation to scar outcome. SNP rs8110090 in TGFβ1 was significantly associated with poorer scar outcomes (p=0.0002). Clinical factors including younger age, shorter time since surgery, and presence of infection or eczema were also associated with worse scarring.

Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.

A case-control study of 326 cases and 748 controls identified 25 SNPs in genes involved in platelet activation, angiogenesis, and inflammatory response that modify the risk of aspirin-related upper gastrointestinal hemorrhage (UGIH). Seven SNPs (rs1387180, rs2238631, rs1799964, rs5050, rs689466, rs1799983, rs7756935) were positive modifiers increasing UGIH risk in aspirin users (RERI 1.75-4.95), while nine SNPs (rs2243086, rs1131882, rs4311994, rs10120688, rs4251961, rs3778355, rs1330344, rs5275, rs3779647) were negative modifiers reducing risk (RERI -2.74 to -0.95). Aspirin exposure alone increased UGIH risk approximately 5.82-fold (95% CI: 2.2-10.08).

This case-control study examined three TNF-α promoter polymorphisms in 331 Korean subjects (123 controls, 208 overweight/obese). The G-238A (rs361525) G/G genotype was significantly more frequent in obese subjects (94.7% vs 85.4%, P=0.0046, OR=3.05), suggesting the G allele is a risk factor for obesity. The C-857T (rs1799724) C allele was associated with higher HDL levels (P=0.014), suggesting a protective effect against atherosclerosis.

This case-control study evaluated 12 SNPs in 8 inflammation-related genes across three studies (Los Angeles, Taixing China, and Memorial Sloan-Kettering) involving 2,049 smoking-related cancer cases and 1,666 controls. IL10 rs1800871 was inversely associated with oropharyngeal cancer (aOR: 0.69, 95% CI: 0.50-0.95) and positively associated with lung cancer among never smokers (aOR: 2.5, 95% CI: 1.3-5.1). TNF rs1799964 was inversely associated with smoking-related cancer in pooled never smokers (aOR: 0.36, 95% CI: 0.17-0.77). After Bayesian correction for multiple comparisons, IL10 rs1800871 and TNF rs1799964 emerged as noteworthy susceptibility markers for smoking-related cancers.

A case-control association study of 2162 Gambian individuals identified a BAT2 polymorphism (rs1046089) significantly associated with severe malaria (G vs A OR=0.73, P<10⁻⁶ for allelic test; recessive model GG vs GA/AA OR=0.48, P<10⁻⁶). Haplotype analysis confirmed BAT2-associated variants conferred ~40% reduced risk. Secondary findings included AIF1 (rs2259571, OR=0.57, P=0.004) and TNF-238 (rs361525, OR=1.33, P=0.04) associations, though only BAT2 remained significant after Bonferroni correction.

This PhD thesis comprises four association studies examining inherited variations in inflammatory cytokine genes and their pathogenetic role in rheumatoid arthritis (RA), multiple myeloma (MM), and B-cell non-Hodgkin's lymphoma (B-NHL). Paper I found that CHI3L1 promoter polymorphisms (rs4950928) were significantly associated with serum YKL-40 concentrations in 238 RA patients (P < 2.0e-16) and 605 controls. Paper IV reported CHI3L1 rs4950928 associated with follicular lymphoma 10-year overall survival (HRCG = 2.04, 95% CI 1.17-3.54). Papers II and III examined gene-gene interactions in MM and B-NHL risk and prognosis.

A large population-based case-control study of TNF-LTA genetic variation in 5,546 breast cancer cases and 5,219 controls (USA and Poland cohorts) found that the variant A allele of rs361525 in the TNF promoter region was associated with modestly increased breast cancer risk (per allele OR=1.18, 95% CI 1.04-1.35, p=0.008). Eight TNF and LTA SNPs were genotyped; haplotype analyses showed the GAG haplotype carrying rs361525 A was associated with elevated risk, while the well-studied TNF-308 variant (rs1800629) showed no association.