Polymorphism rs143384 GDF5 reduces the risk of knee osteoarthritis development in obese individuals and increases the disease risk in non-obese population
Vitaly Novakov,
Olga Novakova,
Maria Churnosova,
Inna Aristova,
Marina Ponomarenko,
Yuliya Reshetnikova,
Vladimir Churnosov,
Inna Sorokina,
Irina Ponomarenko,
Olga Efremova,
Valentina Orlova,
Irina Batlutskaya,
Alexey Polonikov,
Evgeny Reshetnikov,
Mikhail Churnosov
Affiliations
Vitaly Novakov
Department of Medical Biological Disciplines, Belgorod State National Research University
Olga Novakova
Department of Medical Biological Disciplines, Belgorod State National Research University
Maria Churnosova
Department of Medical Biological Disciplines, Belgorod State National Research University
Inna Aristova
Department of Medical Biological Disciplines, Belgorod State National Research University
Marina Ponomarenko
Department of Medical Biological Disciplines, Belgorod State National Research University
Yuliya Reshetnikova
Department of Medical Biological Disciplines, Belgorod State National Research University
Vladimir Churnosov
Department of Medical Biological Disciplines, Belgorod State National Research University
Inna Sorokina
Department of Medical Biological Disciplines, Belgorod State National Research University
Irina Ponomarenko
Department of Medical Biological Disciplines, Belgorod State National Research University
Olga Efremova
Department of Medical Biological Disciplines, Belgorod State National Research University
Valentina Orlova
Department of Medical Biological Disciplines, Belgorod State National Research University
Irina Batlutskaya
Department of Medical Biological Disciplines, Belgorod State National Research University
Alexey Polonikov
Department of Medical Biological Disciplines, Belgorod State National Research University
Evgeny Reshetnikov
Department of Medical Biological Disciplines, Belgorod State National Research University
Mikhail Churnosov
Department of Medical Biological Disciplines, Belgorod State National Research University
Abstract Background We investigated the effect of obesity on the association of genome-wide associative studies (GWAS)-significant genes with the risk of knee osteoarthritis (KOA). Methods All study participants (n = 1,100) were divided into 2 groups in terms of body mass index (BMI): BMI ≥ 30 (255 KOA patients and 167 controls) and BMI < 30 (245 KOA and 433 controls). The eight GWAS-significant KOA single nucleotide polymorphisms (SNP) of six candidate genes, such as LYPLAL1 (rs2820436, rs2820443), SBNO1 (rs1060105, rs56116847), WWP2 (rs34195470), NFAT5 (rs6499244), TGFA (rs3771501), GDF5 (rs143384), were genotyped. Logistic regression analysis (gPLINK online program) was used for SNPs associations study with the risk of developing KOA into 2 groups (BMI ≥ 30 and BMI < 30) separately. The functional effects of KOA risk loci were evaluated using in silico bioinformatic analysis. Results Multidirectional relationships of the rs143384 GDF5 with KOA in BMI-different groups were found: This SNP was KOA protective locus among individuals with BMI ≥ 30 (OR 0.41 [95%CI 0.20–0.94] recessive model) and was disorder risk locus among individuals with BMI < 30 (OR 1.32 [95%CI 1.05–1.65] allele model, OR 1.44 [95%CI 1.10–1.86] additive model, OR 1.67 [95%CI 1.10–2.52] dominant model). Polymorphism rs143384 GDF5 manifested its regulatory effects in relation to nine genes (GDF5, CPNE1, EDEM2, ERGIC3, GDF5OS, PROCR, RBM39, RPL36P4, UQCC1) in adipose tissue, which were involved in the regulation of pathways of apoptosis of striated muscle cells. Conclusions In summary, the effect of obesity on the association of the rs143384 GDF5 with KOA was shown: the “protective” value of this polymorphism in the BMI ≥ 30 group and the “risk” meaning in BMI < 30 cohort.