OBJECTIVE: To estimate whether polymorphisms in the collagen 1Alpha1 gene (COL1Alpha1) and the transforming growth factor-beta gene (TGF-beta;1) are more common in women with cervical insufficiency than in those without the condition. METHODS: Medical, obstetric, and family histories and blood were obtained from women with (n=121) and those without (n=165) cervical insufficiency. DNA was extracted and purified by using commercial DNA isolation kits. Samples were analyzed for variants in two genes, the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphism, by using an allele-specific polymerase chain reaction assay. RESULTS: Thirty-four of 125 (27.2%) women with cervical insufficiency had at least one first-degree female relative affected. The frequency of the homozygous TT genotype in the COL1A1 gene was increased in women with a history of cervical insufficiency compared with controls (10.8% compared with 3.1%, P=.04). The TGF-beta polymorphisms (ArgPro and ProPro) also were increased in cases (38.3% compared with 14.6%, P<.001). CONCLUSION: Over one fourth of women with cervical insufficiency have a family history of cervical insufficiency, and the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphisms are associated with the condition. These observations suggest that, in part, cervical insufficiency is mediated by genetic factors. LEVEL OF EVIDENCE: II.
OBJECTIVE: To estimate whether polymorphisms in the collagen 1Alpha1 gene (COL1Alpha1) and the transforming growth factor-beta gene (TGF-beta;1) are more common in women with cervical insufficiency than in those without the condition. METHODS: Medical, obstetric, and family histories and blood were obtained from women with (n=121) and those without (n=165) cervical insufficiency. DNA was extracted and purified by using commercial DNA isolation kits. Samples were analyzed for variants in two genes, the COL1A1 intron 1SP1 and TGF-betaArg-25-Pro polymorphism, by using an allele-specific polymerase chain reaction assay. RESULTS: Thirty-four of 125 (27.2%) women with cervical insufficiency had at least one first-degree female relative affected. The frequency of the homozygous TT genotype in the COL1A1 gene was increased in women with a history of cervical insufficiency compared with controls (10.8% compared with 3.1%, P=.04). The TGF-beta polymorphisms (ArgPro and ProPro) also were increased in cases (38.3% compared with 14.6%, P<.001). CONCLUSION: Over one fourth of women with cervical insufficiency have a family history of cervical insufficiency, and the COL1A1 intron 1SP1 and TGF-betaArg-25-Pro polymorphisms are associated with the condition. These observations suggest that, in part, cervical insufficiency is mediated by genetic factors. LEVEL OF EVIDENCE: II.
Authors: Seth L Feigenbaum; Yvonne Crites; Mohammad K Hararah; Miya P Yamamoto; Jingrong Yang; Joan C Lo Journal: Hum Reprod Date: 2012-06-14 Impact factor: 6.918