Dinucleotide repeat polymorphism in Fms-like tyrosine kinase-1 (Flt-1) gene is not associated with preeclampsia.
BACKGROUND
Preeclampsia is a major cause of maternal and perinatal mortality and morbidity. The etiology of preeclampsia remains unclear. Recently, it was shown that misregulation of fms-like tyrosine kinase-1 (Flt-1) in the peripheral blood mononuclear cells of pregnant women results in over-expression of the soluble splice variant of Flt-1, sFlt-1, producing an additional (extra-placental) source of sFlt-1 that can contribute to the etiology of preeclampsia. The aim of this study was to investigate the relationship between preeclampsia and a dinucleotide (threonine-glycine; TG)n repeat polymorphism in the 3' non-coding region of the Flt-1 gene.


METHODS
The number of the d(TG)n repeats was analyzed in 170 patients with preeclampsia and in 202 normotensive pregnancies. The region containing the dinucleotide repeat polymorphism of the Flt-1 gene was amplified by polymerase chain reaction (PCR) from the DNA samples and was analyzed by direct PCR sequencing.


RESULTS
We found 10 alleles of the dinucleotide repeat polymorphism and designated these as allele*12 (A1) through allele*23 (A12) according to the number of the TG repeats, from 12 to 23. The frequency of the 14-repeat allele (A3) was most abundant (63.82% in preeclampsia and 69.06% in controls), followed by the 21-repeat allele (A10; 28.53% in preeclampsia and 23.76% in controls). There was no significant difference in the allele frequency between patients with preeclampsia and normal controls. The most common genotype in preeclamptic and normotensive pregnancies was heterozygous (TG)14/(TG)21 (41.76%) and homozygous (TG)14/(TG)14 (45.05%), respectively. However, the genotype frequencies were not significantly different between preeclamptic patients and controls.


CONCLUSIONS
This is the first study to characterize the dinucleotide repeat polymorphism of the Flt-1 gene in patients with preeclampsia. We found no differences in the allele or genotype frequencies between patients with preeclampsia and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the d(TG)n repeat polymorphism of the Flt-1 gene is not associated with the development of preeclampsia in Korean pregnant women.
Kim
Shin-Young
SY
Laboratory of Medical Genetics, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea. chlorella@empal.com
Lim
Ji-Hyae
JH
Yang
Jae-Hyug
JH
Kim
Moon-Young
MY
Han
Jung-Yeol
JY
Ahn
Hyun-Kyong
HK
Choi
Jun-Seek
JS
Park
So-Yeon
SY
Kim
Mi-Jin
MJ
Ryu
Hyun-Mee
HM
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018900:Dinucleotide Repeats / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1