Effects of receptor activator nuclear factor κB gene polymorphisms on the susceptibility to knee osteoarthritis

Abstract

The present study aimed to explore genetic association of receptor activator nuclear factor κB (RANK) polymorphisms with individual susceptibility to knee osteoarthritis (OA) in different Kellgren–Lawrence (KL) grades. This case–control study included 138 knee OA patients and 145 healthy individuals. RANK rs1805034 and rs8086340 polymorphisms were genotyped through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The effects of RANK polymorphisms on knee OA risk were analyzed via χ 2 test or Fisher exact test, and the results were expressed using odds ratios (ORs) with corresponding 95% confidence intervals (CIs). The C allele of rs1805034 polymorphism had significantly higher frequency in knee OA patients than in controls ( P = .044), indicating that this allele could increase the risk of knee OA (OR = 1.424, 95% CI = 1.010–2.008). Besides, the CC genotype and C allele of the rs1805034 polymorphism were significantly associated with elevated risk of knee OA in moderate grade (CC vs TT: P = .018, OR = 3.071, 95% CI = 1.187–7.941; C vs T: P = .012, OR = 1.787, 95% CI = 1.131–2.823). However, rs8086340 polymorphism had no significant association with knee OA risk The C allele of RANK rs1805034 polymorphism is closely correlated with increased risk of knee OA, especially for moderate grade.

Association of RANK and RANKL gene polymorphism with survival and calcium levels in multiple myeloma

“…The exonic SNP rs1805034C>T represents a nonsynonymous alanine ( C ) to valine ( T ) amino acid change (Ala192Val). The C variant was associated with susceptibility to Paget's disease of bone and knee osteoarthritis; conversely, it was found to have a protective role in hip osteoporotic fractures 26–28 . rs1805034 C was also a risk factor in esophageal cancer, but was not associated with risk for breast cancer 22,29,30 .…”

Polymorphisms within the RANK and RANKL Encoding Genes in Patients with Rheumatoid Arthritis: Association with Disease Progression and Effectiveness of the Biological Treatment

“…A very recent study of Yang et al ( 2019 ) documented that RANKL rs2277438 polymorphism increased RA risk, and that the RANK rs1805034 SNP was not related to RA risk. On the other hand, Wang et al ( 2019 ) found the RANK rs1805034 SNP to be associated with susceptibility to knee osteoarthritis.…”

“…The significance of chosen RANK and RANKL single nucleotide polymorphisms (SNPs) have been described before. The role of RANK rs1805034 polymorphism has been analyzed in regard to RA (Mohamed et al 2016 ; Yang et al 2019 ), cancer (Yin et al 2014 ; Zhang et al 2015 ), hip osteoporotic fractures (Zhang et al 2011 ), knee osteoarthritis (Wang et al 2019 ), age at menarche (Duan et al 2015 ; Pan et al 2012 ) and in Paget’s disease (Chung et al 2010 ). The RANK rs8086340 was also previously documented in RA patients, as well as with respect to age at natural menopause (Lu et al 2010 ).…”

RANK/RANKL/OPG gene polymorphisms and loss of orthodontic mini‐implants

“…However, after multivariate analysis, the polymorphism rs8086340 of the RANK gene was associated with the loss of orthodontic MIs. This polymorphism is located in the intron 1 and could have no functional effect on RANK , but it may play a role in the regulation of gene transcription or it may be in LD with other SNPs with potential functional effects . In addition, the C allele of this same polymorphism has also been shown associated with the anticitrullinated peptide antibody present in rheumatoid arthritis in the study of Ruyssen et al…”

“…RANK is a type I transmembrane glycoprotein, generally abundant in osteoclasts and cartilaginous cells, whose gene RANK is located on chromosome 18 in the 18q22.1 region. In addition, it is composed of 12 exons, with an extension of about 80 kb…”