Genetic polymorphism of COL1A1 gene and bone mineralisation in juvenile idiopathic arthritis

Abstract

Objective(s): The aim of our study was to evaluate the role of genetic markers in bone metabolism and mineralization in JIA children. Material & Methods: We included 196 JIA children, 81 boys and 115 girls. Bone mineralization parameters were detected by DXA of lumbar spine L1-L4. Bone biochemical markers were osteocalcin, C-terminal telopeptides (CTT), PTH, Ca, Ca++, P, total alkaline phosphatase (TAP) activity.We have detected Sp1 (rs1800012) and -1997 G/T (rs1107946) polymorphisms in type I (alpha)1 chain collagen gene (COL1A1). Results: We revealed gender differences in Sp1 genotype distribution in children with low BMD (LBMD): boys had GG genotype in 89.5% and girls in 54.2% (p=0.03). In boys GG genotype presence increased LBMD - OR=2.96 (95%CI: 0.59-14.9) compare in girls in which GG presence decreased LBMD - OR=0.56 (95%CI: 0.36-2.7). Also, children carried T allele (GT and TT genotypes) despite on higher inflammatory parameters had better mineralization dates. In total group children with GG genotype had higher osteocalcin (111.0(plus or minus)56.1 ng \ml and 85.9(plus or minus)39.9 ng/ml in GT+TT, p=0.02) and CTT levels (1.22(plus or minus)0.45 ng\ml and 0.99(plus or minus)0.38 ng\ml in GT+TT, p=0.02). In children, who have not been treated with steroids GG genotype was associated with lower BMD Z-score in boys (-1.24(plus or minus)0.14SD and 0.29(plus or minus)0.98SD in GT+TT, p=0.006) and lower height in girls (142.9(plus or minus)28.0 cm and 156.3(plus or minus)21.6 cm in GT+TT, p=0.025). In children with Tanner stage I GG genotype was associated with more rare LBMD (12.8% vs. 36.4% in GT+TT, p=0.05) and with frequent LBMD in children with Tanner stage II-III (37.8% and 5.9% in GT+TT, p=0.01). GG genotype of -1997 G/T polymorphism was associated with lower Ca++ (1.1(plus or minus)0.11 mmol\l and 1.15(plus or minus)0.006 mmol/l in GT+TT, p=0.03), inorganic phosphate (1.67(plus or minus)0.16 mmol/l and 1.57(plus or minus)0.22 mmol/l in GT+TT, p=0.04) and osteocalcin level (82.3(plus or minus)18.4 ng/ml and 115.5(plus or minus)24.2 ng/ml, p=0.01) in children with Tanner stage II-III and lower BMD (0.84(plus or minus)0.14 g\cm2 and 0.91(plus or minus)0.1 in GT+TT, p=0.04) and lower BMD Z-score (-1.275(plus or minus)1.25SD and -0.5(plus or minus)1.0SD in GT+TT, p=0.009) Conclusion(s): We have revealed different changes in mineralization and metabolism, associated with sex, Tanner stage and treatment due to COL1A1 gene polymorphisms in children.