Trisomic pregnancy and intermediate CGG repeat length at the FMR1 locus.
Trisomic pregnancy and intermediate CGG repeat length at the FMR1 locus.
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DOI：
10.1093/humrep/des098
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发表时间：
2012-07
影响因子：
6.1
通讯作者：
Jennie Kline;A. Kinney;Stephen Brown;Bruce Levin;K. Oppenheimer;Dorothy Warburton
中科院分区：
文献类型：
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作者：
Jennie Kline;A. Kinney;Stephen Brown;Bruce Levin;K. Oppenheimer;Dorothy Warburton
背景我们假设三体性的发生是卵母细胞池大小的函数，卵母细胞池减少的妇女风险增加。卵巢池减少可能导致原发性卵巢功能衰竭，这与脆性X染色体智力低下（FMR 1）位点的前突变和中间CGG重复长度有关。因此，我们假设FMR 1基因CGG重复长度中等的女性三体妊娠的风险增加。方法：本分析利用了两项以医院为基础的病例对照研究的数据。我们比较了207例三体自然流产（SA）妇女与三个对照组：82例其他染色体异常SA妇女，99例染色体正常SA妇女和537例活产（LB）妇女，年龄与SA妇女匹配。我们以四种方式定义CGG重复序列的长度：双等位基因平均值、基因型平均值、等位基因2的长度和等位基因1的长度。我们分析了CGG重复长度作为分类变量。所有分析均根据研究中心、年龄和种族进行调整。结果CGG重复序列长度在三体SA患者和三个对照组之间没有显著差异。对于双等位基因平均值，与最高类别（35.5-59.5次重复）和众数类别（26.5-30.0次重复）相关的三体性（与LB对照相比）的校正比值比为1.5（95%置信区间（CI）：0.7，3.1）。与两个SA对照组的比较也显示了三体病例中更多重复的几率增加。当重复长度由基因型平均值或等位基因2上的重复长度定义时，结果相似。对于等位基因1，短（9-19）重复长度的几率较低，但不显着，与LB对照相比，三体病例。从分析中排除有前突变的女性（n= 2），双等位基因平均值的校正比值比为1.4（95% CI：0.7，2.9）。结论我们的数据是模棱两可的。协会的方向是一致的假设，在中间范围内的重复长度与三体性。然而，三体性病例和对照组之间的差异既不大也不具有统计学显著性。我们的数据排除了大于3的优势比。
BACKGROUND We hypothesized that trisomy arises as a function of the size of the oocyte pool, with risk increased among women with diminished pools. Diminished pools may cause primary ovarian failure, which has been associated with premutation and intermediate CGG repeat length at the Fragile X mental retardation (FMR1) locus. Thus, we hypothesized that the risk of trisomic pregnancy is increased among women with intermediate CGG repeat length on the FMR1 gene. METHODS The analysis drew on data from two hospital-based case-control studies. We compared 207 women with trisomic spontaneous abortions (SAs) to three comparison groups: 82 women with other chromosomally abnormal SAs, 99 women with chromosomally normal SAs and 537 women with live births (LBs), age matched to women with SAs. We defined the length of the CGG repeat in four ways: the biallelic mean, the genotypic mean, the length on allele 2 and the length on allele 1. We analyzed CGG repeat length as a categorical variable. All analyses were adjusted for site, age and ethnicity. RESULTS CGG repeat length did not differ significantly between women with trisomic SAs and any of the three comparison groups. For the biallelic mean, the adjusted odds ratio relating trisomy (versus LB controls) to the highest category (35.5-59.5 repeats) versus the modal category (26.5-30.0 repeats) was 1.5 (95% confidence interval (CI): 0.7, 3.1). Comparisons with the two SA control groups also showed increased odds of more repeats among trisomy cases. Results were similar when repeat length was defined by the genotypic mean or by the repeat length on allele 2. For allele 1, the odds of short (9-19) repeat length were lower, but not significantly so, for trisomy cases compared with LB controls. Excluding women with premutations (n= 2) from the analysis yielded an adjusted odds ratio of 1.4 (95% CI: 0.7, 2.9) for the biallelic mean. CONCLUSIONS Our data are equivocal. The direction of associations is consistent with the hypothesis that repeat length in the intermediate range is associated with trisomy. However, differences between the trisomy cases and the comparison groups are neither large nor statistically significant. Our data rule out odds ratios larger than about 3.