Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis

Mónika Mórocz, A. Czibula, Zsuzsanna B. Grózer, Anita Szécsényi, Péter Z. Álmos, I. Raskó, Tamás Illés

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Study Design.: A genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees. Objective.: To reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns. Summary of Background Data.: It was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes. Methods.: The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. Results.: At a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes. Conclusions.: The genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.

Original languageEnglish
JournalSpine
Volume36
Issue number2
DOIs
Publication statusPublished - Jan 15 2011

Fingerprint

Bone Morphogenetic Protein 4
Matrix Metalloproteinase 3
Scoliosis
Leptin
Interleukin-6
Genes
Single Nucleotide Polymorphism
Melatonin MT2 Receptor
Genotype
Bone Remodeling
Genetic Association Studies
Melatonin
Pedigree
Genetic Promoter Regions
Gene Frequency
Osteogenesis
Restriction Fragment Length Polymorphisms
Population
Case-Control Studies
Polymerase Chain Reaction

Keywords

  • Adolescent idiopathic scoliosis
  • association study
  • PCRRFLP
  • promoter polymorphism

ASJC Scopus subject areas

  • Clinical Neurology
  • Orthopedics and Sports Medicine

Cite this

Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. / Mórocz, Mónika; Czibula, A.; Grózer, Zsuzsanna B.; Szécsényi, Anita; Álmos, Péter Z.; Raskó, I.; Illés, Tamás.

In: Spine, Vol. 36, No. 2, 15.01.2011.

Research output: Contribution to journalArticle

Mórocz, Mónika ; Czibula, A. ; Grózer, Zsuzsanna B. ; Szécsényi, Anita ; Álmos, Péter Z. ; Raskó, I. ; Illés, Tamás. / Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis. In: Spine. 2011 ; Vol. 36, No. 2.
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AU - Szécsényi, Anita

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AU - Raskó, I.

AU - Illés, Tamás

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AB - Study Design.: A genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees. Objective.: To reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns. Summary of Background Data.: It was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes. Methods.: The genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. Results.: At a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes. Conclusions.: The genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.

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