Association between Single Nucleotide Polymorphisms of SMAD3 and BMP5 with the Risk of Knee Osteoarthritis
Introduction: The role of genetic factors influencing osteoarthritis (OA) susceptibility is well documented and several candidate genes have been identified to be associated with it. Among these genes are Bone Morphogenetic Protein 5 (BMP5) and Smad family member 3 (SMAD3), all involved in Trans...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
JCDR Research and Publications Private Limited
2017-06-01
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| Series: | Journal of Clinical and Diagnostic Research |
| Subjects: | |
| Online Access: | https://jcdr.net/articles/PDF/10073/22371_CE(RA1)_F(T)_PF1(RU_VT_RB)_PFA(P_RB).pdf |
| Summary: | Introduction: The role of genetic factors influencing osteoarthritis (OA) susceptibility is well documented and several
candidate genes have been identified to be associated with
it. Among these genes are Bone Morphogenetic Protein 5
(BMP5) and Smad family member 3 (SMAD3), all involved in
Transforming Growth Factor (TGF) signaling pathway. The knee
is the commonly affected joint, and knee OA has an especially
high prevalence in Asian population.
Aim: To investigate associations between Single Nucleotide
Polymorphisms (SNPs) rs12901499 in SMAD3 and rs921126
in the BMP5 gene with knee OA susceptibility in and around
Lucknow, Uttar Pradesh, India.
Materials and Methods: SNPs rs12901499 in SMAD3 and
rs921126 in BMP5 were genotyped in patients with knee OA
and age- sex matched OA-free controls from our population.
A total of 450 patients with knee OA and 458 controls were
enrolled in the study. Venous blood samples were obtained from
all cases as well as controls for PCR-RFLP (Polymerase Chain
Reaction- Restriction Fragment Length Polymorphism). Data
was collected and entered in excel sheets. Statistical analyses
of the data were performed using statistical software package
SPSS version 16.0. Chi-square, Student’s t-test and logistic
regression tests were used to analyse the data.
Results: GA and GG genotypes of both SNPs (rs12901499 and
rs921126), and variant G, were associated with a significantly
increased risk of knee OA. A significantly increased risk of knee
OA was associated with the genotype GG and GA of rs12901499
(p < 0.03 and p <0.004 respectively) and rs921126 (p< 0.0001 and
p<0.001 respectively) compared with the AA genotype. In addition,
those bearing at least one G allele (GG + GA) had a significantly
increased risk of knee OA compared with those without the G allele
(AA) in rs921126 (p< 0.0001). However, in rs12901499, significant
association with the risk of knee OA was not found (p<0.4). On age
and gender based stratification, the association between the risk
of OA and rs921126 GG mutant compared with AA homozygotes
was strong in both gender (adjusted OR= 2.93 for male and 2.25 for
female) and in those aged >55 years (adjusted OR= 3.4), similarly
in rs12901499, GG mutant compared with AA homozygote was
strong in female (adjusted OR= 1.5) and in those aged >55 years
(adjusted OR= 1.5).
Conclusion: The results showed that both in SMAD3 rs12901499
and BMP5 921126, G allele is significantly associated with knee
OA. A to G change and variant G genotype may contribute to
knee OA risk in our study population of Lucknow. |
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| ISSN: | 2249-782X 0973-709X |