日本未熟児新生児学会雑誌　第25巻第2号　105～110頁（2013年）

日本未熟児新生児学会雑誌　25(2)：231-236；2013　

受付日：平成24．12．17

受理日：平成25．03．25

日本人small-for-gestational age児における血管内皮増殖因子遺伝子多型の関与の検討

Vascular Endothelial Growth Factor Genetic Polymorphisms in Newborns with Small-for-Gestational Age

＊1神戸大学医学部附属病院　周産母子センター，＊2神戸大学大学院医学研究科　内科系学講座小児科学分野

＊1Center for Perinatal Care，Kobe University Hospital，＊2Department of Pediatrics, Kobe University Graduate School of Medicine

藤岡一路＊1＊2・森岡一朗＊1＊2・長坂美和子＊2・香田　翼＊2・松尾希世美＊2・横田知之＊2・森川　悟＊2・三輪明弘＊1＊2・柴田暁男＊2・山田秀人＊1・飯島一誠＊1＊2

Kazumichi FUJIOKA＊1＊2，Ichiro MORIOKA＊1＊2，Miwako NAGASAKA＊2，Tsubasa KODA＊2， Kiyomi MATSUO＊2，Tomoyuki YOKOTA＊2，Satoru MORIKAWA＊2，Akihiro MIWA＊1＊2， Akio SHIBATA＊2，Hideto YAMADA＊1，Kazumoto IIJIMA＊1＊2

Key Words：allele，genotype，pregnancy induced hypertension，small-for-gestational age，vascular endothelial growth factor

背景：血管内皮増殖因子（VEGF）は，胎生期の血管形成や胎盤血管形成において重要な役割を果たしている。そのVEGF 遺伝子多型は種々の周産期の疾患への関与が報告されているが，small-for-gestational age（SGA）児への関与については明らかではない。
対象・方法：神戸大学病院周産母子センターに入院した初産の新生児のうち，出生体重が在胎週数の平均の発育より-1.5 SD を下回った児41 例をSGA 群，在胎週数通りの発育を遂げた児44 例をAGA 群とした。奇形症候群，染色体異常は除外した。2 群間において，VEGF 遺伝子型を周産期背景因子と共に比較検討した。
結果：2 群間の周産期背景因子は，妊娠高血圧症候群の割合がSGA 群で有意に多かった。VEGF 遺伝子型のアリル頻度は，-1498T＞C のT アリル頻度，-634C＞G のC アリル頻度がSGA 群で有意に高かった。また，遺伝子型頻度は，-1498T＞C のCC 型がSGA 群で有意に少なく，-634C＞G のCC 型がSGA 群で有意に多かった。多変量解析の結果，妊娠高血圧症候群とともに-634C＞G のCC 型がSGA の有意な危険因子であった。
結論：VEGF -634C＞G のCC 型は，SGA の発症に関与している可能性がある。

Background：The etiology of newborns with small-for-gestational age（SGA），who are a primary cause of perinatal morbidity and mortality, is still unclear. Vascular endothelial growth factor（VEGF），a major mediator of vascular permeability and angiogenesis, plays an essential role in fetal angiogenesis and placentogenesis. Genetic polymorphisms in the VEGF gene may contribute to the development of newborns with SGA.
Methods：41 Japanese newborns with SGA and 44 newborns with appropriate-for-gestational age（AGA），who were born from primiparous mothers and admitted to Kobe University Hospital, were included in this study. Newborns with congenital anomalies or congenital chromosomal anomalies were excluded. SGA was defined as birth weight（BW） below -1.5 standard deviation values compared with mean BW of age-matched Japanese newborns. From enrolled newborns, genomic DNA was extracted from umbilical cord, cord blood, or buccal mucosa. Six VEGF genotypes （-1498T>C, -1154G>A, -634C>G, -7C>T, 936C>T, and 1612G>A）were determined by direct DNA sequencing. Clinical perinatal factors, or VEGF allele and genotype frequencies were first evaluated between the groups of newborns with SGA and AGA by an univariate analysis, followed by a multivariate logistic regression analysis. P-values of 0.05 or less were considered to be statistically significant.
Results：Pregnancy induced hypertension（PIH），and VEGF allele frequencies of T in -1498T>C and C in -634C>G in newborns with SGA were significantly higher than those in newborns with AGA. VEGF genotype frequencies of CC in -1498T>C and CC in -634C>G in newborns with SGA had significantly difference in comparison with those in newborns with AGA. In the multivariate logistic regression analysis, PIH and CC in VEGF -634G>C revealed as significant factors associated with newborns with SGA.
Conclusion：We found that Japanese newborns with VEGF -634G>C polymorphisms may be at risk for developing SGA.