rs2228145

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 literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

A genome-wide association study of 83 plasma proteins relevant to cardiovascular disease in 3,394 European subjects identified 79 genome-wide significant loci (p<5e-8), with 55 replicating in independent cohorts (n=2,639). Using eQTL analysis and network methods, the authors proposed plausible causal mechanisms for 25 trans-acting loci including post-translational regulation of KITLG by MMP9 and several receptor-ligand pairs. Multiple loci showed evidence of causal association with coronary artery disease risk.

Case-control study of 292 Colombian subjects (191 dengue cases, 101 controls) evaluating associations between dengue susceptibility and polymorphisms in IL6R (rs8192284), TLR3 (rs3775290), and DC-SIGN (rs7248637). In Afro-Colombians, the C allele of rs8192284 was protective (OR=0.425, p=0.020), while the A alleles of rs7248637 and rs3775290 increased risk (OR=2.389, p=0.015 and OR=2.329, p=0.005 in Mestizos). The CAG allelic combination remained significantly associated with dengue after Amerindian ancestry adjustment (OR=2.16, p=0.028).

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.

Exome sequencing and bioinformatic analysis of 271 Italian samples identified 12 coding variants in IL6 and IL6R genes (rs142759801, rs190436077, rs13306435, rs2228145, and others). Variant impact predictions suggest rs190436077 (p.Glu79Gln) in IL6 and rs2228145 (p.Asp358Ala) in IL6R may alter protein structure and binding properties relevant to COVID-19 severity and neuroinflammatory diseases, with potential pharmacogenetic implications.

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.

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.