title: Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population.
abstract: Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P=0.0007, odds ratio (OR)=1.35 within 95% confidence interval (CI)=1.14-1.61), and individuals with genotype GG had a higher risk for AIS compared with AA+AG (P=0.0001, OR=1.61 within 95% CI=1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P=0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.
authors.affiliation: Spine Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Chen
authors.forename: Nelson L S
authors.initials: NL
authors.lastname: Tang
authors.forename: Xingbin
authors.initials: X
authors.lastname: Cao
authors.forename: Di
authors.initials: D
authors.lastname: Qiao
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.forename: Jack C Y
authors.initials: JC
authors.lastname: Cheng
authors.forename: Yong
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D064236:Cartilage Oligomeric Matrix Protein; D016022:Case-Control Studies; D002648:Child; D002681:China; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D064235:Matrilin Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012600:Scoliosis / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C577539:MATN1 protein, human; C577540:Matn1 protein, mouse; D064235:Matrilin Proteins; C577553:TSP5 protein, human