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目的探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者瘦素受体基因突变与瘦素抵抗的关系。方法应用聚合酶链反应-单链构象多态性(PCR-single strand conformation polymorphism,PCR-SSCP)银染技术结合DNA直接测序,检测PCOS患者33例(PCOS组)及育龄期单纯子宫肌瘤患者33例(对照组)腹壁脂肪组织中瘦素受体(LEPR)基因第2、4、6、7、8、13/14、20外显子的突变。结果共发现24例外显子4上有位置异常的电泳条带,其中PCOS患者18例,对照组6例。经直接测序分析,为A670→G670的纯合多态性突变,即109位氨基酸由赖氨酸(Lys K)置换成精氨酸(ArgR)。PCOS患者的该位点检测到的A→G的多态性变异频率明显高于对照组(P<0.05)。所有检出第4外显子K109R多态性的患者血清瘦素水平高于未检出变异者(P<0.01)。结论 PCOS患者LEPR基因胞外区第4外显子突变频率高于对照组,第4外显子K109R多态性可能与PCOS有遗传倾向的瘦素抵抗有关。
Objective To investigate the relationship between leptin receptor gene mutation and leptin resistance in patients with polycystic ovary syndrome (PCOS). Methods PCR-SSCP and silver direct sequencing were used to detect 33 PCOS patients (PCOS group) and patients with simple myoma of uterus during childbearing age The mutations of leptin receptor (LEPR) gene in exon 2, 4, 6, 7, 8, 13/14 and 20 in abdominal adipose tissue of 33 cases (control group) Results A total of 24 cases of abnormal electrophoresis bands were found on exon 4, including 18 cases of PCOS and 6 cases of control group. After direct sequencing analysis, it was a homozygous mutation of A670 → G670, that is, amino acid 109 was replaced by arginine (ArgR) from lysine (Lys K). The frequency of polymorphism of A → G detected in this site of PCOS patients was significantly higher than that of the control group (P <0.05). Serum leptin level was higher in all patients with exon 4 K109R polymorphism than those without mutation (P <0.01). Conclusions The mutation frequency of exon 4 in extracellular domain of LEPR gene in PCOS patients is higher than that in control group. K109R polymorphism in exon 4 may be associated with leptin resistance with PCOS genetic predisposition.