Association between single nucleotide polymorphism in collagen IX and intervertebral disc disease in the Indian population

Abstract

Background:Symptomatic intervertebral disc degeneration is being recently reported in younger population, questions the basis of its degenerative etiology. Latest evidences show that genetics play a significant role. Collagen IX, an important constituent of disc, is found to be altered in genetically predisposed individuals. Mutations have been reported in COL9A2 and COL9A3 genes, which encode Collagen IX, in Finnish and various other populations. The purpose of the present study is to test the significance of these genes in the Indian population.Materials and Methods:One hundred proven cases of intervertebral disc disease (IDD) of various regions of spine were selected for the study, along with matched controls. They were tested for the above mentioned alleles by allelic discrimination method with real-time polymerase chain reaction (PCR) study after isolation of DNA from blood sample. Each blood sample was classified into one of the three types – homozygous, heterozygous, and wild (normal) type allele – separately for COL9A2 and COL9A3 genes.Results:Homozygosity for COL9A2 allelic variation was associated with 100% occurrence of the disease. Heterozygous allele of COL9A2 was significantly higher in the study group (42%) as compared to the control group (17%). In contrast, allelic variation in COL9A3 gene was found to have no significant correlation with disc disease. There was no single patient with homozygous allelic variation for COL9A3, suggesting predominance of COL9A2 variation in the Indian population.Conclusion:This candidate gene strategy approach adds considerably to our knowledge of genetic makeup of Indian populations in relation with disc disease. This study highlights importance of COL9A2 gene variation especially of homozygous variety in contrast to COL9A3 variation in causing disc disease in Indian population.

Association of collagen I, IX and vitamin D receptor gene polymorphisms with radiological severity of intervertebral disc degeneration in Southern European Ancestor

“…A study from India showed higher frequency of collagen 9a2 heterozygosity in those individuals with disc pathology, despite the absence of a similar association for collagen 9a3 [23] which is in contrast with our findings. This difference may be due to an unidentified genomic factor or another biological pathway, which was not addressed in our study; or this may be related geographical variance of the genomic material and influences of different environmental factors over genes.…”

Association between COL9A2 Gln326Arg mutations and the development of intervertebral disc disease in a Chinese population

“…To date, several studies have tested the association between the COL9A2 gene and development of intervertebral disc disease in various populations (Annunen et al, 1999;Kales et al, 2004;Virtanen et al, 2007;Rathod et al, 2012;Janeczko et al, 2014). Annunen et al (1999) carried out an investigation involving 157 patients and 174 controls, identifying a COL9A2 genetic mutation that cosegregates with the disease phenotype.…”

“…Kales et al (2004) reported that a particular polymorphism of COL9A2 is likely to be a less significant susceptibility factor for the development of intervertebral disc disease in Greek and Finnish populations. Moreover, Rathod et al (2012) revealed that COL9A2 gene variation is a cause of this disease in the Indian population. However, Janeczko et al (2014) found no association between COL9A2 polymorphism and risk of intervertebral disc disease.…”

Degenerated intervertebral disc prolapse and its association of collagen I alpha 1 Spl gene polymorphism

“… 29 A similar association between collagen IX polymorphism and disc degeneration was reported in Indian patients earlier by Rathod et al . 33 However there are no studies to the best of our knowledge assessing COL1A1 polymorphism in Indian patients with IVD degeneration.…”