561例新生儿胰岛素样生长因子-1启动子区域基因多态性观察

Characteristics of polymorphism in promoter region of insulin-like growth factor-1 gene in 561 neonates

目的检测新生儿胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）启动子区域737／738位点胞嘧啶腺苷（cytosine—adenosine，CA）重复序列的基因多态性。方法选择2010年6月1日至2012年6月30日于北京大学第三医院出生的健康新生儿561例。记录新生儿的性别、出生胎龄、出生体重、身长，并进行胎龄评估。出生后3～5d清晨空腹采集足跟血，提取DNA，分析IGF-1启动子区域基因多态性。采用y。检验、独立样本t检验、方差分析和Hardy—Weinberg平衡检验进行统计学分析。结果561例新生儿中，足月儿413例，早产儿148例；大于胎龄儿92例，适于胎龄儿433例，小于胎龄儿36例。561例共发现7种不同的等位基因及23种不同的基因型。7种等位基因分别为188、190、192、194、196、198和200bp。最常见的3种基因型为190～192bp、192～196bp及192～192bp，其频率分别为23．2％（130／561）、15．0％（84／561）和12．8％（72／561）。CA19纯合基因型（CA19／CA19）、CA19杂合基因型（CA19／CAn019）及CA19突变基因型（CAn019／CAno19）的频率在足月儿和早产儿之间差异均无统计学意义[分别为11．4％（47／413）与16．9％（25／148）、55．9％（231／413）与50．7％（75／148）、32．7％（135／413）与32．4％（48／148），X^2=2．96、1．21和0．00，P均〉0．05]。CA19／CA19、CA19／cAn019、CAn019／cAn019这3种基因型新生儿的出生胎龄分别为（37．1±2．9）、（37．6±3．1）和（37．4±3．1）周，差异无统计学意义（F=0．54，P=0．58）。CA19／CA19在小于胎龄儿中的频率明显高于大于胎龄儿及适于胎龄儿[分别为25．0％（9／36）、7．6％（7／92）及12．9％（56／433），X^2=7．01，P；0．03]，但CA19／CAnol9及cAnol9／CAn019基因型频率在大于胎龄儿、适于胎龄儿及小于胎龄儿3组之间差异无统计学意义（CA19／CAn019：X^2=1．13，P-0．57；CAn019／CAno19;X^2=0．58，P=0．75）。结论IGF-1启动子区存在基因多态性，CA19等位基因频率与出生胎龄无关。

Objective To investigate polymorphism in the promoter region of insulin-like growth factor-1（IGF-1） gene. Methods Five hundred and sixty one neonates admitted to Peking University Third Hospital from June 1st, 2010 to June 30th, 2012 were recruited into the study. Gender, gestational age, birth weight and birth length were collected. Heel blood samples were collected on 3-5 days after birth. DNA was extracted to analyze the polymorphism in the promoter region of IGF-1 gene. Chi-square test, independent-sample t-test, analysis of variance and Hardy- Weinberg equilibrium were performed. Results Among the 561 neonates, 413 were full term, and 148 were preterm; 92 were large for gestational age （LGA）, 433 were appropriate for gestional age （AGA）, and 36 were small for gestional age （SGA）. Seven different alleles and 23 genotypes in the promoter region of IGF-1 gene were identified in the population. The seven alleles were 188, 190, 192, 194, 196, 198 and 200 bp respectively. The three most common genotypes were 190-192 bp, 192-196 bp and 192-192 bp, whose frequencies were 23.2% （130/561）, 15.0% （84/561） and 12.8% （72/561）. There were no significant differences of cytosine-adenosine （CA）19/CA19, CA19/CAno19 and CAno19/CAno19 genotypes between full term and preterm infants [-11.4% （47/413） vs 16.9% （25/148）, 55.9% （231/413） vs 50.7% （75/148） and 32.7N （135/413） vs 32.4N （48/148） respectively, X^2 =2.96, 1.21 and 0.00, all P〉0. 051. There was no difference in the gestional age among infants with CA19/CA19, CA19/CAno19 and CAno19/CAno19 genotypes [（37.1 ± 2.9）, （37.6±3. 1） and （37.4± 3.1） weeks respectively, F = 0.54, P = 0. 581. The frequency of CA19/ CA19 in SGA neonates was higher than that in LGA and AGA neonates [-25.0% （9/36） vs 7.6% （7/92） and 12.9% （56/433）,）X^2 = 7.01, P= 0.03], but there were no differences in the frequency of CA19/CAno19 and CAno19/CAno19 among LGA, AGA and SGA neonates （CA19/CAno19;X^2 = 1.13, P=0. 57;CAno19/CAno19 ,X^2 =0.58, P=0.75）. Conclusions Polymorphism exists in the promoter region of IGF-1 gene. The gestational age is not associated with the frequency of CA19 allele.