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Role of resistin genetic variations in knee osteoarthritis pathogenesis, a cross sectional study

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Abstract

Osteoarthritis (OA) is a serious health concern globally and is recognized by degradation of articular cartilage, bone remodeling and synovial inflammation. Resistin is an adipokine that shown to be involved in inflammatory process associated with OA. Aim of the current study was to estimate the link of resistin gene polymorphisms (− 420 C>G, + 299 G>A) with genetic susceptibility of knee OA in a Pakistani population. 280 patients and 308 age and sex matched controls were recruited in this case-control study. Genotype and allele frequencies were evaluated by Polymerase chain reaction-Restriction Fragment Length Polymorphism. Resistin concentration was measured by immunoassay. A significant difference in allele and genotype frequency was observed for both study groups. Resistin − 420 mutant genotype was associated with an increased susceptibility to OA (p = 0.001). Similarly, resistin + 299 GA + AA genotypes showed a relation with an elevated risk of knee OA compared to GG genotype (p = 0.01). Moreover, the mutant alleles frequency was significantly high in patient group as compared to healthy individuals for both loci (p < 0.01). Resistin − 420/+ 299 alleles haplotype analysis demonstrated that mutant alleles were more prevalent in OA affected individuals compared to healthy subjects (p < 0.05). The serum resistin levels were not remarkably different in patient vs. control group (p = 0.9). Further, the circulating resistin level was not found to be influenced by − 420G and + 299A alleles and non significant differences were observed in resistin concentration in mutant vs. wild type genotypes for both SNPs (p > 0.05). Our data suggest an association between investigated resistin genetic variants and knee OA susceptibility in our population. This is the first report to show association between investigated single nucleotide polymorphisms and OA among any population.

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References

  1. Naqvi SKB, Bibi M, Murtaza I, Javed Q (2019) Interleukin-6 (-572) and tumor necrosis factor α (-308 and -238) polymorphisms and risk of knee osteoarthritis in a Pakistani population: a case–control study. Iran J Sci Technol Trans Sci. https://doi.org/10.1007/s40995-019-00678-5

    Article  Google Scholar 

  2. Sobhan MR, Mehdinejad M, Jamaladini MH, Mazaheri M, Zare-Shehneh M, Neamatzadeh H (2017) Association between aspartic acid repeat polymorphism of the aspirin gene and risk of knee osteoarthritis: a systematic review and meta-analysis. Acta Orthop Traumatol Turc 51(5):001. https://doi.org/10.1016/j.aott.2017.08

    Article  Google Scholar 

  3. Sobhan MR, Mahdinezhad-Yazdi M, Jafari M, Mazaheri M, Neamatzadeh H, Daliri K (2018) Association of ESRα XbaI A>G, Pvu II T>C and ESRβ AlwNI T>C polymorphisms with the risk of adolescent idiopathic scoliosis: a systematic review and genetic metaanalysis. Rev Bras Ortop (English Ed) https://doi.org/10.1016/J.RBOE.2018.03.001

    Article  Google Scholar 

  4. Han L, Song JH, Yoon JH, Paer YG, Lee SW, Choi YJ et al (2012) TNF-a and TNF-β polymorphisms are associated with susceptibility to osteoarthritis in a Korean population. Korean J Pathol 46(1):30–37

    Article  Google Scholar 

  5. Solokov J, Lepus CM (2013) Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Adv Musculoskel Dis 7:77–94

    Google Scholar 

  6. Orita S, Koshi T, Mitsuka T, Miyagi M, Inoue G, Arai G et al (2011) Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet Disord 12(1):144

    Article  CAS  Google Scholar 

  7. de Lange-Brokaar BJ, Ioan-Facsinay A, Osch GJVM et al (2012) Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthr Cartil 20:1484–1499

    Article  Google Scholar 

  8. Bassiouni H (2015) Detection of changes in the serum and synovial fluid levels of resistin during flare ups and remissions in primary knee osteoarthritis. Arthritis Rheumatol 67: (suppl 10)

  9. Koskinen A, Vuolteenaho K, Moilanen T, Moilanen E (2014) Resistin as a factor in osteoarthritis: synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases MMP-1 and MMP-3. Scand J Rheumatol 43:249–253

    Article  CAS  Google Scholar 

  10. Song YZ, Guan J, Wang HJ, Ma W, Li F, Xu F et al (2015) Possible involvement of serum and synovial fluid resistin in knee osteoarthritis: cartilage damage, clinical, and radiological links. J Clin Lab Anal 30(5):437–443

    Article  Google Scholar 

  11. Fioravanti A, Cheleschi S, De Palma A, Addimanda O, Mancarella L et al (2018) Can adipokines serum levels be used as biomarkers of hand osteoarthritis? Biomarkers 23(3): 265–270

    Article  CAS  Google Scholar 

  12. Taka EK, Manolakis AC, Kapsoritakis AN, Potamianos SP (2011) The implication of adiponectin and resistin in gastrointestinal diseases. Cytokine Growth Factor Rev 22(2):109–119

    Article  Google Scholar 

  13. Sood A, Shore SA (2013) Adiponectin, leptin, and resistin in asthma: basic mechanisms through population studies. J Allergy. https://doi.org/10.1155/2013/785835

    Article  Google Scholar 

  14. Fioravanti A, Giannitti C, Cheleschi S, Simpatico A, Pascarelli NA, Galeazzi, Mal (2015) Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis. Int J Biometeorol 59(11):1691–1700

    Article  Google Scholar 

  15. Zhang Z, Xing X, Hensley G, Chang LW, Liao W, Abu-Amer Y et al (2010) Resistin induces expression of proinflammatory cytokines and chemokines in human articular chondrocytes via transcription and messenger RNA stabilization. Arthritis Rheum 62:1993–2003

    Article  CAS  Google Scholar 

  16. Nogueiras R, Novelle MG, Vazquez MJ, Lopez M, Dieguez C (2009) Resistin: regulation of food intake glucose homeostasis lipid metabolism. Endocr Dev 17:175–184

    Article  Google Scholar 

  17. Pan SS, Le YY (2006) Role of resistin in inflammation and inflammation-related diseases. Cell Mol Immunol 3(1):29–34

    Google Scholar 

  18. Lee SE, Kim HS (2012) Human resistin in cardiovascular disease. J Smooth Muscle Res 48(1):27–35

    Article  CAS  Google Scholar 

  19. Filkova M, Haluzik M, Gay S, Senolt L (2009) The role of resistin as a regulator of inflammation: implications for various human pathologies. Clin J Immunol 133(2):157–170

    Article  CAS  Google Scholar 

  20. Choe JY, Bae J, Jung HY, Park SH, Lee HJ, Kim SK (2012) Serum resistin level is associated with radiographic changes in hand osteoarthritis: cross-sectional study. Joint Bone Spine 79(2):160–165

    Article  CAS  Google Scholar 

  21. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A (2005) Resistin, an adipokine with potent proinflammatory properties. J Immunol 74:5789–5795

    Article  Google Scholar 

  22. Perruccio AV, Mahomed NN, Chandran V, Gandhi R (2014) Plasma adipokine levels and their association with overall burden of painful joints among individuals with hip and knee osteoarthritis. J Rheum 41(2):334–337

    Article  CAS  Google Scholar 

  23. Filkova M, Liskova M, Hulejova H et al (2009) Increased serum adiponectin levels in female patients with erosive compared with non-erosive osteoarthritis. Ann Rheum Dis 68(2):295–296

    Article  CAS  Google Scholar 

  24. Osawa H, Yamada HK, Onuma H et al (2004) The G/G genotype of a resistin single-nucleotide polymorphism at − 420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3. Am J Hum Genet 75(4):678–686

    Article  CAS  Google Scholar 

  25. Hussain S, Bibi S, Javed Q (2011) Heritability of genetic variants of resistin gene in patients with coronary artery disease: a family-based study. Clin Biochem 44(8):618–622

    Article  CAS  Google Scholar 

  26. Tang NP, Wang LS, Yang L et al (2008) A polymorphism in the resistin gene promoter and the risk of coronary artery disease in a Chinese population. Clin Endocrinol 68(1):82–87

    Article  CAS  Google Scholar 

  27. Suriyaprom K, Tungtrongchitr R, Namjuntra P (2014) Associations of resistin levels with resistin gene polymorphism and metabolic syndrome in thais. J Med Biochem 34(2):170 – 178

    Article  Google Scholar 

  28. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M et al (1986) Development of criteria for the classification and reporting of steoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29:1039–1049

    Article  CAS  Google Scholar 

  29. Senolt L, Housa D, Vernerova Z, Jirasek T, Svobodova R, Veigl D et al (2007) Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann Rheum Dis 66(4):458–463

    Article  CAS  Google Scholar 

  30. Lehrke M, Reilly MP, Millington SC, Iqbal N, Rader DJ, Lazar MA (2004) An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 1(2):e45

    Article  Google Scholar 

  31. Tarkowski A, Bjersing J, Shestakov A, Bokarewa MI (2010) Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med 14:1419–1431

    Article  CAS  Google Scholar 

  32. Presle N, Pottie P, Dumond H et al (2006) Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis, contribution of joint tissues to their articular production. Osteoarthr Cartil 14(7):690–695

    Article  CAS  Google Scholar 

  33. Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C (2008) Osteoarthritis and obesity: experimental models. Joint Bone Spine 75(6):675–679

    Article  Google Scholar 

  34. Gegout PP, Francin PJ, Mainard D, Presle N (2008) Adipokines in osteoarthritis: friends or foes of cartilage homeostasis. Joint Bone Spine 75(6):669–671

    Article  Google Scholar 

  35. Lee JH, Ort T, Ma K, Picha K, Carton J, Marsters PA et al (2009) Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro. Osteoarthr Cartil 17(5):613–620

    Article  CAS  Google Scholar 

  36. Li XC, Tian F, Wang F (2014) Clinical significance of resistin expression in osteoarthritis: a meta-analysis. Biomed Reserch intl 2014:208016

    Google Scholar 

  37. Marwa MEA, Naglaa FG, Abeer S, Maha MH, Lamees MD, Mohamed MEA (2016) Association of the RETN − 420 C > G polymorphism with rheumatoid arthritis in an Egyptian population. Int J Curr Microbiol App Sci 5(11):183–195

    Article  Google Scholar 

  38. Takhshid MA, Zare Z (2015) Resistin − 420 C/G polymorphism and serum resistin level in Iranian patients with gestational diabetes mellitus. J Diabetes Metab Disord 14:37–43

    Article  Google Scholar 

  39. Hussain S, Asghar M, Javed Q (2010) Resistin gene promoter region polymorphism and the risk of hypertrophic cardiomyopathy in patients. Transl Res 155(3):142–147

    Article  CAS  Google Scholar 

  40. Onuma H, Tabara Y, Kawamura R, Tanaka T, Ohashi J, Nishida W et al (2010) A at single nucleotide polymorphism-358 is required for G at − 420 to confer the highest plasma resistin in the general Japanese population. PLoS ONE 5(3):e9718

    Article  Google Scholar 

  41. Suriyaprom K, Phonrat B, Namjuntra P, Chanchay S, Tungtrongchitr R (2009) The + 299 (G > A) resistin gene polymorphism and susceptibility to type 2 diabetes in Thais. J Clin Biochem Nutr 44(1):104–110

    Article  CAS  Google Scholar 

  42. Lau CH, Muniandy S (2011) Adiponectin and resistin gene polymorphisms in association with their respective adipokine levels. Ann Hum Genet 75:370–382

    Article  CAS  Google Scholar 

  43. Zayani N, Hamdouni H, Boumaiza I, Achour O, Neffati F, Omezzine A et al (2018) Resistin polymorphims, plasma resistin levels and obesity in Tunisian volunteers. J Clin Lab Anal 32(2): https://doi.org/10.1002/jcla.22227

  44. Yoshimura Y, Nishii S, Zaima N, Moriyama T, Kawamura Y (2013) Ellagic acid improves hepatic steatosis and serum lipid composition through reduction of serum resistin levels and transcriptional activation of hepatic ppara in obese, diabetic KK-A(y) mice. Biochem Biophys Res Commun 434(3):486–491

    Article  CAS  Google Scholar 

  45. Menzaghi C, Trischitta V (2010) Genetics of serum resistin: a paradigm of population-specific regulation? Diabetologia 53(2):226–228

    Article  CAS  Google Scholar 

  46. Kunnari A, Ukkola O, Kesaniemi AY (2005) Resistin polymorphisms are associated with cerebrovascular disease in Finnish type 2 diabetic patients. Diabet Med 22(5):583–589

    Article  CAS  Google Scholar 

  47. Asano H, Izawa H, Nagata K, Nakatochi M, Kobayashi M, Hirashiki A et al (2010) Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population. Diabetologia 53(2):234–246

    Article  CAS  Google Scholar 

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Correspondence to Iram Murtaza or Qamar Javed.

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Naqvi, S.K.B., Murtaza, I. & Javed, Q. Role of resistin genetic variations in knee osteoarthritis pathogenesis, a cross sectional study. Mol Biol Rep 46, 2657–2663 (2019). https://doi.org/10.1007/s11033-019-04673-2

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