Multifactorial Landscape Parses to Reveal a Predictive Model for Knee Osteoarthritis.

The present study attempted to investigate whether concerted contributions of significant risk variables, pro-inflammatory markers, and candidate genes translate into a predictive marker for knee osteoarthritis (KOA). The present study comprised 279 confirmed osteoarthritis patients (Kellgren and Lawrence scale >2) and 287 controls. Twenty SNPs within five genes (CRP, COL1A1, IL-6, VDR, and eNOS), four pro-inflammatory markers (interleukin-6 (IL-6), interleuin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP)), along with significant risk variables were investigated. A receiver operating characteristic (ROC) curve was used to observe the predictive ability of the model for distinguishing patients with KOA. Multivariable logistic regression analysis revealed that higher body mass index (BMI), triglycerides (TG), poor sleep, IL-6, IL-1ß, and hsCRP were independent predictors for KOA after adjusting for the confounding from other risk variables. Four susceptibility haplotypes for the risk of KOA, AGT, GGGGCT, AGC, and CTAAAT, were observed within CRP, IL-6, VDR, and eNOS genes, which showed their impact in recessive ß(SE): 2.11 (0.76), recessive ß(SE): 2.75 (0.59), dominant ß(SE): 1.89 (0.52), and multiplicative modes ß(SE): 1.89 (0.52), respectively. ROC curve analysis revealed the model comprising higher values of BMI, poor sleep, IL-6, and IL-1ß was predictive of KOA (AUC: 0.80, 95%CI: 0.74-0.86, p< 0.001), and the strength of the predictive ability increased when susceptibility haplotypes AGC and GGGGCT were involved (AUC: 0.90, 95%CI: 0.87-0.95, p< 0.001).This study offers a predictive marker for KOA based on the risk scores of some pertinent genes and their genetic variants along with some pro-inflammatory markers and traditional risk variables.

Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women.

The present study aimed to examine the participation and contribution of endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE) and vascular endothelial growth factor (VEGFA) genes for the risk of endothelial dysfunction (ED)-associated osteoporosis risk in postmenopausal women of Punjab, India. Women with ED were categorized into women with osteoporosis (n = 346) and women without osteoporosis (n = 330). They were examined for selected SNPs within eNOS, ACE and VEGFA genes. Linear regression analysis revealed a positive association of ED with bone mineral densities (BMDs) at femoral neck (r2 = 0.78, p < 0.001) and lumbar spine (r2 = 0.24, p = 0.001) after Bonferroni correction. Three susceptibility haplotypes were exposed within eNOS (CTAAAT), ACE (ACDG) and VEGFA (GATA) genes. Bearers of CTAAAT (OR 2.43, p = 0.007), ACDG (OR 2.50, p = 0.002) and GATA (OR 2.10, p = 0.009) had substantial impact for osteoporosis after correcting the effects with traditional risk factors (TRD).With uncertainty measure (R2h) and Akaike information criterion (AIC), best fit models showed that CTAAAT manifested in multiplicative mode (ß ± SE: 2.19 ± 0.86, p < 0.001), whereas ACDG (ß ± SE: 1.73 ± 0.54, p = 0.001) and GATA (ß ± SE: 3.07 ± 0.81, p < 0.001) expressed in dominant modes. Area under receiver operating characteristic curve using weighted risk scores (effect estimates) showed substantial strength for model comprising TRD + GATA (AUC = 0.8, p < 0.001) whereas, model comprising TRD + GATA + CTAAAT exhibited excellent ability to predict osteoporosis (AUC = 0.824, p < 0.001).

Investigation of eNOS gene polymorphism exposes a genetic association between endothelial dysfunction and osteoporosis in postmenopausal women.

OBJECTIVES: To investigate the association of genetic polymorphisms of endothelial nitric oxide synthase (eNOS) gene with endothelial dysfunction associated osteoporosis in postmenopausal women of Punjab, India. METHODS: The study involved 456 postmenopausal women having endothelial dysfunction categorized according to women with (n = 236) and without osteoporosis (n = 220). Bone mineral density (BMD) and reactive hyperemia index (RHI) were evaluated together with six single-nucleotide polymorphisms (SNPs) within the eNOS gene (rs2070744, rs1799983, rs1800780, rs3918181, rs891512, and rs1808593). RESULTS: A moderate association between RHI and BMD at femoral neck (r = 0.213, P = 0.002) and lumbar spine (r = 0.267, P < 0.001) was observed. Minor alleles C and T of SNPs rs2070744 and rs1799983 were associated with chances of osteoporosis in both co-dominant (odds ratio [OR] 2.13, P = 0.017; OR 2.77, P = 0.009) and dominant (OR 2.10, P = 0.011; OR 2.45, P = 0.007) modes, whereas minor allele A of SNP rs891512 showed marginal probability in dominant model (OR 1.68, P = 0.047). A susceptibility haplotype (CTAAAT) was observed within the eNOS gene which conferred 2.32 times higher chances of osteoporosis (OR 2.32, 95% confidence interval 1.18-4.54, P = 0.021) after adjusting for the effect of confounders. Genetic model analysis revealed that each copy of susceptibility haplotype increased the possibility of osteoporosis by a factor of 2.11 ±â€Š0.63 (P < 0.001). RHI was significantly associated with susceptibility haplotype CTAAAT in a dose-dependent manner, whereby the severity of endothelial dysfunction increased significantly in women having two copies over women having one copy or no copy (ß = 2.13, P < 0.001) of susceptibility haplotype. CONCLUSION: A susceptibility haplotype CTAAAT within the eNOS gene is associated with double the possibility of endothelial dysfunction affiliated osteoporosis in postmenopausal women of Punjab, India.