瘦素受体基因变异与中国人肥胖的关系

Variation of the human leptin receptor gene in obese Chinese population

目的 研究瘦素受体基因变异与中国人肥胖的关系。方法 选择肥胖病人〔体重指数(BMI)≥ 30kg/m2 〕和正常人 (BMI <2 5kg/m2 )各 5 0例 ,抽提基因组DNA ;用PCR SSCP技术筛查瘦素受体基因外显子 1～ 7、12和 18及内含子 2的变异。结果 在瘦素受体基因内含子 2处发现有碱基改变 (T→C) ;瘦素受体基因外显子 18发现碱基改变 (C→A) ,导致其 96 8位氨基酸由丙氨酸→天冬氨酸。结论 瘦素受体基因内含子 2发生碱基改变可能引起瘦素受体基因RNA剪切异常 ,导致产生异常的瘦素受体 ;瘦素受体基因外显子 18碱基改变 ,导致其 96 8位氨基酸由丙氨酸→天冬氨酸 ,氨基酸改变可能影响受体的空间构象 。

Objective To investigate the relationship between the genetic variation of leptin receptor and obesity in Chinese population. Methods Genomic DNA was extracted from 50 obese subjects 〔Body mass index (BMI)≥30 kg/m 2〕 and 50 normal individuals (BMI<25 kg/m 2) by standard methods; primer pairs for PCR SSCP specific to the genomic sequence of exon 1 7, 12, 18 and intron 2 were synthesized and PCR SSCP was conducted to screen sequence variation. Results Variations in intron 2 (T→C) and in exon 18 (C→A) were found and the latter caused an amino acid variation (Ala→Asp). Conclusions The variation in intron 2 may result in abnormal splicing of leptin receptor gene RNA. The amino acid variation (Ala→Asp) in leptin receptor exon 18 may influence its conformation and function.