Association of Adam 12 variants with osteoarthritis in an urban South African population

DG Sengwayo; F Mashinya; T Chikowore; M Lukhele; S Motaung

DG Sengwayo Tshwane University of Technology https://orcid.org/0000-0002-6966-509X
F Mashinya Institute of Bio Research Auditing and Training in Southern Africa https://orcid.org/0000-0002-4132-7558
T Chikowore University of the Witwatersrand https://orcid.org/0000-0002-6743-751X
M Lukhele University of the Witwatersrand https://orcid.org/0000-0001-9114-8200
S Motaung Durban University of Technology https://orcid.org/0000-0001-8503-9868

Keywords: metalloproteinase, single-nucleotide, polymorphism, genotypes alleles

Abstract

Background: Osteoarthritis (OA) is a multifactorial, progressive, and degenerative disease of the synovial joints. A Disintegrin and Metalloproteinase Domain 12 (ADAM 12) gene variants have been associated with osteoarthritis in Asians and Europeans, but not in the African populations. We therefore examined the association of osteoarthritis with ADAM12 gene variants rs1278279, rs3740199, rs1044122 and rs1871054 in South African population.

Methods: A cross-sectional, case control study conducted amongst 377 South Africans, consisting of 136 OA cases and 241 non-OA controls. A questionnaire was used for demographic data collection. Anthropometry variables were measured using standard methods. DNA samples were genotyped using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The standard models of genetic association were used to evaluate the effect of ADAM12 variants on OA risk. The multivariate test using logistic regression was conducted on selected variants while adjusting for age, sex and BMI.

Results: A unit increase in body mass index (BMI) increased the likelihood of OA by 1.12 times (P<0.001) and 1.13 times (P= 0.026) amongst black and white participants, respectively. A unit increase in age increased the likelihood of OA by 1.10 times (P<0.001) amongst black participants. Men sex significantly reduced the risk of OA by 0.58 times amongst black participants. Of the four ADAM12 variants, rs1871054 was associated with an increase in OA risk only in white South Africans, before (P=0.008) and after (P=0.036), adjusting for age, sex and BMI.

Conclusion: The findings of this study suggest the need for ethnic-specific variants to assess the genetic susceptibility of OA in black South African population.

Author Biographies

DG Sengwayo, Tshwane University of Technology

Department of Biomedical Sciences, Faculty of Science, Tshwane University of Technology, South Africa

F Mashinya, Institute of Bio Research Auditing and Training in Southern Africa

Institute of Bio Research Auditing and Training in Southern Africa, South Africa

T Chikowore, University of the Witwatersrand

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand and MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, South Africa

M Lukhele, University of the Witwatersrand

Division of Orthopaedics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, South Africa

S Motaung, Durban University of Technology

Technology Transfer and Innovation, Durban University of Technology, South Africa