Genetic susceptibility of lumbar degenerative disc disease in young Indian adults View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-11-22

AUTHORS

S. Rajasekaran, Rishi Mugesh Kanna, Natesan Senthil, Muthuraja Raveendran, Veera Ranjani, Kenneth M. C. Cheung, Danny Chan, Patrick Y. P. Kao, Anita Yee, Ajoy Prasad Shetty

ABSTRACT

PurposeAlthough 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.MethodsPatients (<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).Results695 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.ConclusionThe study identifies specific SNP associations of five genes in young adults with severe lumbar disc degeneration. These five genes (COL11A1, ADAMTS5, CALM1, IL1F5and 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. More... »

PAGES

1969-1975

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00586-014-3687-y

DOI

http://dx.doi.org/10.1007/s00586-014-3687-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006587671

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25416170


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39 COX2
40 IL1F5
41 Indian adults
42 Indian subjects
43 L1
44 MRI
45 MethodsPatients
46 Pfirrmann grading
47 Results695 Indian subjects
48 S1
49 SNP associations
50 TDDS
51 adults
52 age
53 analysis
54 association
55 association analysis
56 candidate genes
57 candidate genes viz
58 cascade
59 complex diseases
60 degeneration
61 degenerative disc disease
62 degenerative score
63 different functions
64 disc degeneration
65 disc degenerative score
66 disc disease
67 disease
68 disk
69 exact mechanism
70 exact role
71 function
72 genes
73 genes viz
74 genetic association analysis
75 genetic influences
76 genetic polymorphisms
77 genetic predisposition
78 genetic susceptibility
79 grading
80 group
81 group A
82 group B
83 identifies specific SNP associations
84 individual disks
85 inflammatory cascade
86 influence
87 interplay
88 intracellular signaling
89 intricate interplay
90 lumbar disc degeneration
91 lumbar spine
92 matrix metabolism
93 mean age
94 mechanism
95 metabolism
96 mild TDDS
97 multiple genetic polymorphisms
98 nucleotide polymorphisms
99 patients
100 polymorphism
101 predisposition
102 role
103 rs1337185
104 rs1337185 of COL11A
105 rs162509
106 rs162509 of ADAMTS5
107 rs3213718
108 rs3213718 of CALM1
109 rs5275
110 rs5277
111 rs7575934
112 rs7575934 of IL1F5
113 scores
114 severe TDDS
115 severe lumbar disc degeneration
116 severity
117 severity of DDD
118 signaling
119 significant genetic influence
120 single nucleotide polymorphisms
121 specific SNP associations
122 spine
123 study identifies specific SNP associations
124 subjects
125 susceptibility
126 viz
127 years
128 young Indian adults
129 young adults
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