title: Genetic susceptibility of lumbar degenerative disc disease in young Indian adults.
abstract: OBJECTIVE
  Although the exact mechanisms that lead to degenerative disc disease (DDD) are not well understood, a significant genetic influence has been found. Focusing on DDD that occurs in young adults can be valuable in determining the exact role of genetic predisposition to DDD.
  
  
  METHODS
  Patients (<40 years) with lumbar disc degeneration were evaluated with MRI imaging (1.5 Tesla) and genetic association analysis for 58 single nucleotide polymorphism (SNP) of 35 candidate genes was performed. Disc degeneration of individual discs of lumbar spine from L1 to S1 was graded by Pfirrmann's grading. The subjects were stratified into two groups based on Total Disc Degenerative Score (TDDS). Based on TDDS, the severity of DDD was classified as mild (Group A: TDDS <10) and severe (Group B: TDDS >10).
  
  
  RESULTS
  695 Indian subjects including 308 with mild TDDS and 387 with severe TDDS were studied. The mean age of the patients was 29.6 ± 6.9 years in group A and 31.7 ± 6.1 in group B (p < 0.05). Five of the 35 candidate genes viz., rs1337185 of COL11A (p = 0.02), rs5275 (p = 0.03) and rs5277 (p = 0.05) of COX2, rs7575934 of IL1F5 (p = 0.04), rs3213718 of CALM1 (p = 0.04) and rs162509 of ADAMTS5 (p = 0.04) were found to be significantly associated with severe TDDS.
  
  
  CONCLUSIONS
  The study identifies specific SNP associations of five genes in young adults with severe lumbar disc degeneration. These five genes (COL11A1, ADAMTS5, CALM1, IL1F5 and COX2) have different functions in the matrix metabolism, intracellular signalling and inflammatory cascade. This shows that disc degeneration is a complex disease with an intricate interplay of multiple genetic polymorphisms.
authors.affiliation: Department of Orthopaedics and Spine Surgery, Ganga Hospital, 313, Mettupalayam Road, Coimbatore, Tamil Nadu, 641 011, India, sr@gangahospital.com.
authors.forename: S
authors.initials: S
authors.lastname: Rajasekaran
authors.forename: Rishi Mugesh
authors.initials: RM
authors.lastname: Kanna
authors.forename: Natesan
authors.initials: N
authors.lastname: Senthil
authors.forename: Muthuraja
authors.initials: M
authors.lastname: Raveendran
authors.forename: Veera
authors.initials: V
authors.lastname: Ranjani
authors.forename: Kenneth M C
authors.initials: KM
authors.lastname: Cheung
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
authors.forename: Patrick Y P
authors.initials: PY
authors.lastname: Kao
authors.forename: Anita
authors.initials: A
authors.lastname: Yee
authors.forename: Ajoy Prasad
authors.initials: AP
authors.lastname: Shetty
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000071116:ADAMTS5 Protein; D000328:Adult; D002147:Calmodulin / Q000235:genetics; D024161:Collagen Type XI / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D007378:Interleukins / Q000235:genetics; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C574182:COL11A1 protein, human; D002147:Calmodulin; D024161:Collagen Type XI; C122187:IL36RN protein, human; D007378:Interleukins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human