MKRN3基因rs2239669多态性与中枢性性早熟易感性的相关性研究

Association of ring-finger protein 3(MKRN3) gene rs2239669 polymorphism with central precocious puberty susceptibility

目的探讨makorin环指蛋白3(MKRN3)基因的多态性位点rs2239669与中枢性性早熟(CPP)易感性的关系。方法采用病例-对照研究方法,选取246例CPP患儿为研究对象,以269例健康儿童作为对照组。利用高分辨率溶解曲线(HRM)和实时定量-聚合酶链反应(RT-PCR)方法,对rs2239669位点多态性和MKRN3基因表达水平进行检测,比较不同基因型、等位基因及其在不同基因模型中与CPP风险的关系,以及不同基因型的MKRN3基因表达水平。结果 CPP组SNP位点rs2239669的基因型(TT、TC、CC)频率与对照组的差异有统计学意义(P=0.035);CC基因型的CPP发病风险是TT基因型的2.298倍(95%CI:1.045~5.051)。CPP组C等位基因频率高于对照组(78.7%对71.7%,P=0.010);携带C等位基因患CPP风险是T等位基因的1.451倍(95%CI:1.090~1.932)。在隐性遗传模型中,CC基因型在CPP组明显高于对照组(P=0.021)。在三种基因型的CPP患儿中,每种各随机抽取9例,比较MKRN3表达水平发现其差异有统计学意义(F=4.052,P=0.041)。结论 MKRN3基因SNP位点rs2239669变异与CPP遗传易感性相关,不同基因型CPP患儿的MKRN3表达水平有差异。

Objectives To explore the association between the single nucleotide polymorphism （SNP） rs2239669 in makorin ring-finger protein 3 （MKRN3） gene and the susceptibility to central precocious puberty （CPP）. Methods A case-control study including 246 children with CPP and 269 healthy children was performed. The genotype and MKRN3 expression levels of patients were analyzed by PCR-HRM and RT-PCR,respectively. Results SNP rs2239669 genotype （TT,TC,CC） and allele frequencies （T and C） were different between cases and controls,with higher CC genotype in CPP patients. Under recessive model （CC/TT＋TC）,CC genotype was higher in CPP group and associated with higher risk of CPP （95%CI：1.062-2.143, P=0.021）. MKRN3 expression levels were different among patients with different genotypes,of which TT genotype had the highest level followed by TC and CC （0.376±0.094, 0.330±0.068, 0.250±0.072, P=0.041）. Conclusions MKRN3 SNP rs2239669 was associated with increased risk of CPP, and patients with TT genotype had higher MKRN3 levels.