中国妊娠期血糖异常人群葡萄糖激酶基因突变初步筛查

Preliminary screening of mutations in the glucokinase gene in Chinese gestational subjects with abnormal glucose metabolism

目的 初步明确中国妊娠期血糖异常人群中葡萄糖激酶（GCK）基因突变情况.方法 回顾性选择2005年7月至2008年5月在北京协和医院进行妊娠期血糖筛查并进行了口服葡萄糖耐量试验（OGTT）和糖化血红蛋白（HbA1c）检测的妊娠妇女.以空腹血糖在5.5～ 10.0 mmol/L、OGTT试验2h与0h血糖差值小于4.6 mmol/L且HbA1c值小于8.0％作为筛选条件,对满足所有条件者进行GCK基因外显子区和启动子区-71G＞C的突变筛查.结果 共纳入577例受试者,符合GCK基因检测条件者30例,可获得标本数17例,发现1例GCK基因突变致青少年的成人起病型糖尿病2型（MODY2）患者和1处非编码区新变异.该MODY2患者6号外显子区c.626 C＞T（NM_000162.3）突变导致第209位编码氨基酸从苏氨酸变为甲硫氨酸（p.T209M,NP_000153.1）.推测中国妊娠期血糖异常人群GCK最小突变率为0.27％,估测中国总人群中MODY2的最小患病率为21/10万.结论 中国妊娠期血糖异常的人群中GCK基因突变并不常见.

Objective To preliminarily assess the rate of glucokinase （GCK） gene mutation in Chinese gestational subjects with abnormal glucose metabolism.Methods We retrospectively analyzed Chinese gestational subjects who received oral glucose tolerance test and glycosylated hemoglobin A1c （HbA1c） detection in Peking Union Medical College Hospital （PUMCH） from July 2005 to May 2008.Subjects were selected for direct sequencing of GCK gene if they met the following three criteria：（1） fasting plasma glucose was between 5.5 and 10.0 mmol/L; （2） a small increase （〈 4.6 mmol/L） in plasma glucose 2 hours after an oral glucose load ; （3） HbA1 c was below 8.0%.Results A total of 577 subjects were collected in this study,in which 30 subjects met the criteria for GCK gene mutation testing.Of the 17 subjects whose DNA samples were obtainable,one case of maturity-onset diabetes of the young type 2 （MODY2） with GCK gene mutation c.626 C 〉 T（NM_000162.3） in exon6 and one case with previously unreported variation in noncoding region had been found.The mutation c.626C 〉 T（NM_000162.3） resulted in the substitution of methionine for threonine in amino acid 209 （p.T209M,NP_000153.1）.It was estimated the minimum GCK gene mutation rate was 0.27% in Chinese gestational subjects with abnormal glucose metabolism,and the minimum prevalence of MODY2 was 21/100 000 in Chinese population.Conclusion The GCK gene mutations are not common in Chinese gestational subjects with abnormal glucose metabolism.