Differential association of DENND1A genetic variants with polycystic ovary syndrome in Tunisian but not Bahraini Arab women
Differential association of DENND1A genetic variants with polycystic ovary syndrome in Tunisian but not Bahraini Arab women
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DOI：
10.1016/j.gene.2018.01.028
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发表时间：
2018-03-20
期刊：
影响因子：
3.5
通讯作者：
Almawi, Wassim Y.
中科院分区：
文献类型：
--
作者：
Dallel, Meriem;Sarray, Sameh;Almawi, Wassim Y.
背景和目的：多囊卵巢综合征（PCOS）是一种常见的内分泌疾病，是由可改变和不可改变因素（包括遗传倾向）相互作用引起的。之前的全基因组关联研究和荟萃分析将 DENND1A 确定为某些人群（但并非所有人群）中的 PCOS 易感基因座。我们调查了突尼斯和巴林阿拉伯女性之间 DENNDIA 基因变异与 PCOS 的关联是否相似。 对象和方法：这是回顾性病例对照研究。研究对象包括 320 名患有 PCOS 的女性和 446 名年龄和种族匹配的对照女性。通过实时 PCR 对 DENNDIA rs10818854、rs2479106 和 rs10986105 变体进行基因分型。结果：rs10818854 和 rs10986105 DENND1A 变体的次要等位基因频率在 PCOS 女性中显着较高。以纯合野生型基因型携带者为参考，rs10818854和rs10986105与PCOS风险增加相关，在控制关键协变量后这种风险持续存在，而在加性模型下仅rs2479106可见PCOS风险降低。这分别将 PCOS 的易感性和保护性赋予了这些基因型。 rs10818854 和 rs10986105 均与 PCOS 女性的 HOMA-IR 和 AMH 呈正相关。 Haploview 分析显示所测试的 DENNDIA 变体之间存在有限的连锁不平衡。单倍型分配存在广泛的多样性，大多数单倍型 (99.5%) 由 5 个单倍型捕获。以 GAT 单倍型为参考，AAG 和 GAG 单倍型与 PCOS 呈正相关，而 GAT 单倍型与 PCOS 呈负相关。结论：DENNDIA rs10818854 和 rs10986105 变异与突尼斯女性而非巴林女性 PCOS 的关联证实了这种关联与研究对象的民族/种族血统的依赖性。
Background and aim: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and results from interaction between modifiable and non-modifiable factors, including genetic predisposition. Previous genomewide association studies and meta-analysis identified DENND1A as PCOS susceptibility locus in some, but not all populations. We investigated whether the association of DENNDIA gene variants with PCOS was similar between Tunisian and Bahraini Arab women.Subjects and methods: This was retrospective case-control study. Study subjects comprised 320 women with PCOS, and 446 age-and ethnically-matched control women. Genotyping of DENNDIA rs10818854, rs2479106, and rs10986105 variants was done by real-time PCR.Results: Minor allele frequency of rs10818854 and rs10986105 DENND1A variants were significantly higher among women with PCOS. Setting homozygous wild-type genotype carrier as reference, rs10818854 and rs10986105 were associated with increased risk of PCOS, which persisted after controlling for key covariates, while reduced PCOS risk was seen with only rs2479106 under the additive model. This assigned PCOS susceptibility and protective nature to these genotypes, respectively. Both rs10818854 and rs10986105 were positively associated with HOMA-IR and AMH in women with PCOS. Haploview analysis revealed limited linkage disequilibrium between the tested DENNDIA variants. Extensive diversity in haplotypes assignment was seen, with most haplotypes (99.5%) captured by 5 haplotypes. Taking GAT haplotype as reference, AAG, and GAG haplotypes were positively, while GAT haplotype was negatively associated with PCOS.Conclusion: The association of DENNDIA rs10818854 and rs10986105 variants with PCOS in Tunisian but not Bahraini women confirms the dependence of this association on the ethnic/racial origin of study subjects.