Analysis of Single Nucleotide Polymorphism in Adolescent Idiopathic Scoliosis in Korea: For Personalized Treatment

다국어 초록 (Multilingual Abstract)

Purpose: The incidence of adolescent idiopathic scoliosis (AIS) has rapidly increased,and with it, physician consultations and expenditures (about one and a half times) in the last 5 years. Recent etiological studies reveal that AIS is a complex genetic disorder that results from the interaction of multiple gene loci and the environment.
For personalized treatment of AIS, a tool that can accurately measure the progression of Cobb’s angle would be of great use. Gene analysis utilizing single nucleotide polymorphism (SNP) has been developed as a diagnostic tool for use in Caucasians but not Koreans. Therefore, we attempted to reveal AIS-related genes and their relevance in Koreans, exploring the potential use of gene analysis as a diagnostic tool for personalized treatment of AIS therein. Materials and Methods: A total of 68 Korean AIS and 35 age- and sex-matched, healthy adolescents were enrolled in this study and were examined for 10 candidate scoliosis gene SNPs. Results:This study revealed that the SNPs of rs2449539 in lysosomal-associated transmembrane protein 4 beta (LAPTM4B) and rs5742612 in upstream and insulin-like growth factor 1 (IGF1) were associated with both susceptibility to and curve severity in AIS. The results suggested that both LAPTM4B and IGF1 genes were important in AIS predisposition and progression. Conclusion: Thus, on the basis of this study, if more SNPs or candidate genes are studied in a larger population in Korea, personalized treatment of Korean AIS patients might become a possibility.

참고문헌 (Reference)

1 Chen WJ, "Vitamin D receptor gene polymorphisms: no association with low bone mineral density in adolescent idiopathic scoliosis girls" 46 : 1183-1186, 2008

2 Ward K, "Validation of DNA-based prognostic testing to predict spinal curve progression in adolescent idiopathic scoliosis" 35 : E1455-E1464, 2010

3 Wang WJ, "Top theories for the etiopathogenesis of adolescent idiopathic scoliosis" 31 (31): S14-S27, 2011

4 Yawn BP, "The estimated cost of school scoliosis screening" 25 : 2387-2391, 2000

5 Fei Q, "The association analysis of TBX6 polymorphism with susceptibility to congenital scoliosis in a Chinese Han population" 35 : 983-988, 2010

6 Renshaw TS, "Screening school children for scoliosis" (229) : 26-33, 1988

7 "Scoliosis is increasing in teenager from 2006 to 2010 in Republic of Korea" Press report in Korea health insurance review and assessment service

8 Chen Z, "Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population" 17 : 525-532, 2009

9 Peterson LE, "Prediction of progression of the curve in girls who have adolescent idiopathic scoliosis of moderate severity. Logistic regression analysis based on data from The Brace Study of the Scoliosis Research Society" 77 : 823-827, 1995

10 Suh KT, "Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis" 19 : 1545-1550, 2010

11 Ward K, "Polygenic inheritance of adolescent idiopathic scoliosis: a study of extended families in Utah" 152A : 1178-1188, 2010

12 Zhou L, "Overexpression of LAPTM4B-35 attenuates epirubucin-induced apoptosis of gallbladder carcinoma GBC-SD cells" 150 : 25-31, 2011

13 Qiu XS, "Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis" 32 : 1748-1753, 2007

14 Takahashi Y, "Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B, TPH1, and IGF1 in a Japanese population" 29 : 1055-1058, 2011

15 Suh SW, "Idiopathic scoliosis in Korean schoolchildren: a prospective screening study of over 1 million children" 20 : 1087-1094, 2011

16 Miller NH, "Identification of candidate regions for familial idiopathic scoliosis" 30 : 1181-1187, 2005

17 Sharma S, "Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes" 20 : 1456-1466, 2011

18 Gurnett CA, "Genetic linkage localizes an adolescent idiopathic scoliosis and pectus excavatum gene to chromosome 18 q" 34 : E94-E100, 2009

19 Cheng JC, "Genetic association of complex traits: using idiopathic scoliosis as an example" 462 : 38-44, 2007

20 Cheng JC, "Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis" 15 : 1587-1595, 2000

21 Rahman T, "Electronic monitoring of scoliosis brace wear compliance" 4 : 343-347, 2010

22 Kleinerman RA, "Cancer risks following diagnostic and therapeutic radiation exposure in children" 36 (36): 121-125, 2006

23 Katz DE, "Brace wear control of curve progression in adolescent idiopathic scoliosis" 92 : 1343-1352, 2010

24 Mórocz M, "Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis" 36 : E123-E130, 2011

25 Lee WT, "Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls" 16 : 1924-1932, 2005

26 Barrios C, "Anthropometry and body composition profile of girls with nonsurgically treated adolescent idiopathic scoliosis" 36 : 1470-1477, 2011

27 Andersen MO, "Adolescent idiopathic scoliosis in twins: a population-based survey" 32 : 927-930, 2007

28 Ogilvie J, "Adolescent idiopathic scoliosis and genetic testing" 22 : 67-70, 2010

29 Weinstein SL, "Adolescent idiopathic scoliosis" 371 : 1527-1537, 2008

30 Siu King Cheung C, "Abnormal peri-pubertal anthropometric measurements and growth pattern in adolescent idiopathic scoliosis: a study of 598 patients" 28 : 2152-2157, 2003

31 Liu Z, "Abnormal leptin bioavailability in adolescent idiopathic scoliosis: an important new finding" 37 : 599-604, 2012