title: An SNP of the ZBTB38 gene is associated with idiopathic short stature in the Chinese Han population.
abstract: OBJECTIVE
  Idiopathic short stature (ISS) refers to extreme short stature without any diagnostic explanation. Recently, three genome-wide association studies discovered associations between the ZBTB38 and adult height in different populations. Therefore, variations in the ZBTB38 might contribute to ISS. Furthermore, one study in Korean population showed that ZBTB38 gene was significantly associated with adult height, but not with ISS. We want to examine whether the variants in ZBTB38 are associated with ISS in Chinese Han.
  
  
  METHODS
  A case-control association study was performed in 268 ISS patients and 513 healthy controls from Chinese Han population. Fourteen tag SNPs were selected and genotyped using SNaPshot method. Furthermore, expression of mRNA was quantified by RT-qPCR, and assessment of allelic expression imbalance was conducted with SNaPshot method.
  
  
  RESULTS
  Seven ZBTB38 SNPs were significantly associated with ISS by allele tests (rs724016, rs1582874, rs11919556, rs6440006, rs7612543, rs62282002, rs18651435). And five loci were associated with ISS according to genotype (rs11919556, rs16851419, rs6440006, rs62282002, rs18651435). Notably, after applying the stringent Bonferroni correction for multiple testing, one SNP, rs16851435, remained significantly associated by allele and genotype (P = 5·30 × 10⁻⁴ for allele and P = 0·002 for genotype). Furthermore, the rs16851435 alleles were investigated association with ZTBT38 mRNA expression levels. The G allele showed a higher transcriptional activity than the T allele (P = 0·002).
  
  
  CONCLUSIONS
  Our study indicated that the nonsynonymous SNP (rs16851435:T > G,p.Ser319Ala) of ZBTB38 was contributed to susceptibility of ISS in the Chinese Han population.
authors.affiliation: School of Medicine, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU), Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Wang
authors.forename: Yue-chun
authors.initials: YC
authors.lastname: Teng
authors.forename: Jin-xiu
authors.initials: JX
authors.lastname: Shi
authors.forename: Hai-feng
authors.initials: HF
authors.lastname: Wang
authors.forename: Wen-tao
authors.initials: WT
authors.lastname: Yuan
authors.forename: Xun
authors.initials: X
authors.lastname: Chu
authors.forename: De-fen
authors.initials: DF
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D001827:Body Height; D016022:Case-Control Studies; D002648:Child; D002681:China; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins; C508975:ZBTB38 protein, human