Study On The Genetic Loci Of Idiopathic Spontaneous Abortion

Background: Spontaneous Abortion (SA) is the most common obstetrical diseases. Traditionally, SA is clinically characterized by the loss of≥3 consecutive pregnancies. At present, however, many clinicians and investigators define SA as≥2 consecutive losses. The etiology of recurrent miscarriage (SA) is extremely heterogeneous, including genetic, immunologic, anatomic, endocrinological, infectious anomalies etc. However, about 50% of SA is poorly understood, which is called idiopathic spontaneous abortion (ISA). To identify the genetic loci that might harbor genes predisposed to ISA and provided new insights for future genetic- and etiological-study of ISA, we performed a genome-wide association study.Materials and methods: Forty-four patients with ISA (≥2 consecutive spontaneous abortions occurring before 12 weeks'gestation) and Forty-four sex- and ethnic-matched healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral venous blood leukocytes of each subject, and then was adjusted to 20 ng/ul. Case-DNA- and control-DNA-pool (with equality of individual DNA quantity) were constructed from 44 patients and 44 controls, respectively. In addition, fluorescence-tagged (6-FAM, VIC, NED) 430 microsatellite markers (400 markers with an average spacing of 10 cM are distributed throughout the whole genome; 30 markers with an average spacing of 5 cM are across the whole X chromosome) were purchased from Applied Biosystems. We use a two-stage approach in this work. Firstly, DNA pooling method was used as an initial screen. Secondly, positive markers obtained from DNA pooling were selected for further individual genotyping in each case- and control-subject to confirm ISA the reliability of the differentiating alleles that were first identified using the pooled DNA method.Results: Three loci, 6q27 (D6S446, P=0.028), 9q33.1 (D9S1776, P=0.037) and Xp22.11 (DXS1226, P=0.008), significantly associated with ISA were identified.Conclusion: This is the first genome-wide association study to search for predisposing genes of ISA. The results were preliminary in nature because of the small number of cases and controls and the limited number of markers. Further studies to replicate our findings in another cohort with a larger sample and more markers are required.