**12. Cartilage oligomeric matrix protein** *(COMP)* **gene**

Briggs *et al*. [129] demonstrated that the *COMP* gene contains 19 exons. Exons 4-19, which encode the EGF-like (type II) repeats, calmodulin-like (type III) repeats (CLRs), and the C-terminal domain, correspond in sequence and intron location to the thrombospondin genes, whereas exons 1-3 are unique to *COMP.* Mabuchi *et al.* [130] reported that hereditary osteochondral dysplasia produces severe earlyonset OA Among them are Pseudochondroplasia (PSACH) & multiple epiphyseal dysplasias (MED) both of which are caused by a mutation in the *COMP* gene. Therefore *COMP* may be a susceptibility gene for OA. For these reasons, Mabuchi *et al*. [131] hypothesized that Osteoarthritis is a common disorder may be at the mild end of the phenotypic gradation produced by *COMP* mutations. They ascertained the sequences of the exons and exon-intron boundaries and identified 16 polymorphisms in the *COMP* gene. Using five polymorphisms spanning the entire *COMP* gene (−1417 C/G in promoter region with P = 0.29, c.279C/A in exon 4 with P = 0.19, IVS5 + 76 T/C with P = 0.74, IVS16-45C/T with P = 0.19 and IVS18-40 T/C with P = 0.93), Mabuchi et al. [132], examined the association of this gene in Japanese patients with Osteoarthritis of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were significantly different between osteoarthritis and control groups, and with the help of this study, they hypothesize that comp gene is a candidature gene for OA Song *et al*. [133] identified mutations in the *COMP* gene in 9 of 9 Korean patients with PSACH and 3 of 5 Korean patients with MED. Three of the eight mutations identified were novel. Deere *et al.* identified 12 mutations in the *COMP* gene, including ten novel mutations in 12 patients with PSACH. The site of the mutations emphasized the importance of the calcium-binding domains and

**237**

**Author details**

Lucknow, UP, India

Saloni Raj2

Rajeshwar Nath Srivastava1

and Lavini Raj3

2 Westminster College, Utah, USA

provided the original work is properly cited.

\*, Amar Chandra Sharma1

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

An extensive literature search, we could find only one more study conducted in Indian population other than ours, by Subramanyam et al. They studied the association of rs73297147 and rs73771337 polymorphisms in COL2A1 and CRTL1 genes with primary KOA in South Indian population, and a significant association was observed.

the globular domain to the function of COMP. Kennedy *et al.* reported three SNPs in *COMP*, first in exon-11, nucleotide change A>G at c1156 with allelic frequency 0.03, second in exon −16, nucleotide change G>A at c17.55 with allelic frequency 0.05, and last third one is in 3'UTR, Nucleotide change A>G at c2289 with allelic frequency

CALM1 gene showed a significant association of SNP with the disease. CALM1 gene intronic SNP (rs3213718) was present in our population, and its occurrence

A case-control study of 600 subjects showed a significant association of the+104 T/C GDF5 polymorphism with KOA and with individual clinical symptoms of the disease. A study done by **Srivastava et al.** reported that genetic polymorphisms affecting KOA vary between genders and indicate a role for BMP5, COL2A1, CCL2, and IL1B in North Indian Population. Another case-control study of 499 KOA cases and 458 controls exhibited an association between rs1470527, rs9382564 polymorphisms of BMP5 gene with KOA. This association was validated by haplotype analysis.

Further, the association between KOA and rs1470527 polymorphism was more robust in both the genders and age groups. However, association with rs9382564 was stronger only in female patients and either gender aged >55 years. Moreover, our data showed a significant association of both SNPs with VAS and WOMAC clinical scores. Furthermore, a genetic study conducted in our laboratory on SNPs rs921126 (BMP5) and rs12901499 (SMAD3) showed a significant association between these SNPs and risk of KOA. It was found that the risk increased with age (>55) in both the genders. We also conducted a pilot study on VDR gene polymorphism and its association with KOA. It was found that Taq1 polymorphism influenced the clinico-radiological response to vitamin D supplementation in KOA subjects with insufficient 25(OH) vitamin D levels. Validation of the results is in process on large

1 Department of Orthopaedic Surgery, King George's Medical University,

3 Hult International Business School, San Francisco, USA

population with insufficient 25(OH) vitamin D levels.

\*Address all correspondence to: drrnsrivastava@yahoo.com

, Sudeepti Ratan Srivastava1

,

*Genetics in Osteoarthritis Knee*

*DOI: http://dx.doi.org/10.5772/intechopen.93890*

0.005 which are associated with OA [133].

was significantly affecting the disease**.**

#### *Genetics in Osteoarthritis Knee DOI: http://dx.doi.org/10.5772/intechopen.93890*

the globular domain to the function of COMP. Kennedy *et al.* reported three SNPs in *COMP*, first in exon-11, nucleotide change A>G at c1156 with allelic frequency 0.03, second in exon −16, nucleotide change G>A at c17.55 with allelic frequency 0.05, and last third one is in 3'UTR, Nucleotide change A>G at c2289 with allelic frequency 0.005 which are associated with OA [133].

CALM1 gene showed a significant association of SNP with the disease. CALM1 gene intronic SNP (rs3213718) was present in our population, and its occurrence was significantly affecting the disease**.**

A case-control study of 600 subjects showed a significant association of the+104 T/C GDF5 polymorphism with KOA and with individual clinical symptoms of the disease. A study done by **Srivastava et al.** reported that genetic polymorphisms affecting KOA vary between genders and indicate a role for BMP5, COL2A1, CCL2, and IL1B in North Indian Population. Another case-control study of 499 KOA cases and 458 controls exhibited an association between rs1470527, rs9382564 polymorphisms of BMP5 gene with KOA. This association was validated by haplotype analysis. Further, the association between KOA and rs1470527 polymorphism was more robust in both the genders and age groups. However, association with rs9382564 was stronger only in female patients and either gender aged >55 years. Moreover, our data showed a significant association of both SNPs with VAS and WOMAC clinical scores.

Furthermore, a genetic study conducted in our laboratory on SNPs rs921126 (BMP5) and rs12901499 (SMAD3) showed a significant association between these SNPs and risk of KOA. It was found that the risk increased with age (>55) in both the genders. We also conducted a pilot study on VDR gene polymorphism and its association with KOA. It was found that Taq1 polymorphism influenced the clinico-radiological response to vitamin D supplementation in KOA subjects with insufficient 25(OH) vitamin D levels. Validation of the results is in process on large population with insufficient 25(OH) vitamin D levels.

An extensive literature search, we could find only one more study conducted in Indian population other than ours, by Subramanyam et al. They studied the association of rs73297147 and rs73771337 polymorphisms in COL2A1 and CRTL1 genes with primary KOA in South Indian population, and a significant association was observed.
