An SNP of the ZBTB38 gene is associated with idiopathic short stature in the Chinese Han population

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 x 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.