Association analysis of polymorphisms rs12997 in ACVR1 and rs1043784 in BMP6 genes involved in bone morphogenic protein signaling pathway in primary angle-closure and pseudoexfoliation glaucoma patients of Saudi origin.

4区 医学 Q4 Medicine
Altaf A Kondkar, Tahira Sultan, Taif A Azad, Essam A Osman, Faisal A Almobarak, Saleh A Al-Obeidan
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引用次数: 9

Abstract

Background: Glaucoma is a polygenic neurodegenerative disease and the second most common cause of blindness in Saudi Arabia. To test the hypothesis that genetic variants in the genes involved in the bone morphogenic protein (BMP) signaling pathway may be associated with glaucoma, we investigated the association between 3' untranslated region variants, rs12997 in ACVR1 and rs1043784 in BMP6, and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG).

Methods: In a case-control study, TaqMan® real-time PCR-based genotyping was done in 444 subjects consisting of 250 controls, 101 PACG and 95 PXG cases, and tested for genetic association with glaucoma-types and other clinical phenotypes.

Results: Rs12997[G] allele in ACVR1 exhibited significant 2-fold increased risk of PACG (p = 0.005) in women but not in men. Similarly, genotype analysis also showed that subjects carrying rs12997[G/G] genotype were at > 2-fold risk of PACG that remained significant after adjustment for age, sex, and Bonferroni correction in the recessive model. Furthermore, this effect was also significant in women only. In PXG, the rs12997[G/G] genotype showed a significant trend towards increased risk of the disease (OR = 2.04, 95% CI = 0.99-4.18, p = 0.049) but did not survive the Bonferroni correction. Regression analysis showed that rs12997[G/G] genotype was a significant predictor of PACG independent of age, sex, and rs1043784 genotypes. Likewise, age and rs12997[G/G] genotype showed significant effect on PXG outcome. The rs12997[A/G] genotype showed significant association with cup/disc ratio as compared to wild-type (p = 0.005) in PXG. Genotype and allele frequencies of rs1043784 in BMP6 did not show any significant association either with PACG or PXG.

Conclusions: Our results suggest that the polymorphism rs12997 in the ACVR1 gene involved in the BMP signaling pathway is significantly associated with PACG and PXG in a Saudi cohort. This is the first study to associate this variant/gene with PACG and PXG. However, further studies would be needed to replicate these findings in a large population-based cohort.

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与骨形态发生蛋白信号通路相关的BMP6基因ACVR1 rs12997和rs1043784多态性与沙特原发原发性闭角和假脱落性青光眼患者的关联分析
背景:青光眼是一种多基因神经退行性疾病,是沙特阿拉伯第二大致盲原因。为了验证骨形态发生蛋白(BMP)信号通路相关基因的遗传变异可能与青光眼有关的假设,我们研究了3'非翻译区变异ACVR1中的rs12997和BMP6中的rs1043784与原发性闭角型青光眼(PACG)和假脱落性青光眼(PXG)之间的关系。方法:在一项病例对照研究中,对444名受试者(包括250名对照组、101名PACG和95名PXG)进行TaqMan®实时pcr基因分型,并检测其与青光眼类型和其他临床表型的遗传相关性。结果:ACVR1基因Rs12997[G]等位基因在女性中增加2倍的PACG风险(p = 0.005),而在男性中没有增加。同样,基因型分析也显示,携带rs12997[G/G]基因型的受试者发生PACG的风险大于2倍,在隐性模型中调整年龄、性别和Bonferroni校正后,这一风险仍然显著。此外,这种效应仅在女性中也很显著。在PXG中,rs12997[G/G]基因型显示出疾病风险增加的显著趋势(OR = 2.04, 95% CI = 0.99-4.18, p = 0.049),但未在Bonferroni校正中存活。回归分析显示,rs12997[G/G]基因型是PACG的显著预测因子,与年龄、性别和rs1043784基因型无关。同样,年龄和rs12997[G/G]基因型对PXG结局也有显著影响。与野生型相比,rs12997[A/G]基因型与杯盘比显著相关(p = 0.005)。BMP6中rs1043784基因型和等位基因频率与PACG和PXG均无显著相关性。结论:我们的研究结果表明,参与BMP信号通路的ACVR1基因rs12997多态性与沙特队列中的PACG和PXG显著相关。这是首次将该变异/基因与PACG和PXG联系起来的研究。然而,需要进一步的研究来在大规模的人群队列中复制这些发现。
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来源期刊
BMC Medical Genetics
BMC Medical Genetics 医学-遗传学
自引率
0.00%
发文量
0
审稿时长
12 months
期刊介绍: BMC Medical Genetics is an open access journal publishing original peer-reviewed research articles in the effects of genetic variation in individuals, families and among populations in relation to human health and disease. Note: BMC Medical Genetics is now closed. This journal has merged with BMC Medical Genomics, a broad-scope, open access community journal for all medical genetics and genomics research.
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