在孟加拉国人群中,截断变异rs373056577增加了2型糖尿病的风险,错义变异rs121912717与高甘油三酯血症相关

Shomoita Sayed , Abdullah Al Saba , Imrul Hasan , Rafia Rahat , Mohammad Sayem , Akio Ebihara , A.H.M. Nurun Nabi
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引用次数: 0

摘要

本研究探讨了APOA1和APOA2基因中rs121912717和rs373056577等位基因和基因型变异与2型糖尿病(T2D)风险的关系。在本横断面研究中,采用特异性Taqman探针的实时定量PCR测定了300名孟加拉国无亲缘关系个体(健康= 144,T2D患者= 156)rs121912717和rs373056577的基因型和等位基因频率。采用Logistic回归分析研究不同遗传模式下这些snp的基因型和等位基因频率与T2D的关系。APOA1内rs121912717的等位基因频率和基因型频率均未显示与T2D有显著关联。APOA2中rs373056577基因型在共显性杂合模型(GG vs GA) [OR (95% CI): 2.64 (1.32-5.59), p = 0.008]、显性模型[OR (95% CI): 2.31 (1.24-4.49), p = 0.01]和过显性模型[OR (95% CI): 2.62 (1.31-5.53), p = 0.008]下与T2D风险显著相关,不考虑年龄、性别和BMI。在调整年龄、性别和BMI后,rs373056577等位基因A与T2D仅在优势模型中显示显著相关[OR (95% CI): 3.20 (1.12-10.51), p = 0.04]。此外,与等位基因G相比,rs373056577等位基因A与T2D风险显著相关[OR (95% CI): 2.90 (1.15-8.14), p = 0.03],且未调整混杂因素[OR (95% CI): 1.97 (1.14-3.52), p = 0.02]。在对rs373056577进行性别分层分析时,基因型频率与男性参与者共显性、显性和过显性模型中的T2D显著相关。然而,当对年龄和BMI进行调整的逻辑回归分析时,在任何模型中,关于男性参与者的rs373056577的关联都不显著。另一方面,性别分层回归分析显示,rs121912717的等位基因和基因型频率在调整年龄和BMI前后与T2D无显著相关性。无论是否调整研究参与者的年龄、性别、BMI和疾病状态,rs121912717 CT基因型个体的甘油三酯水平(322.2 mg/dL)明显高于CC基因型个体(202.8 mg/dL)。综上所述,本研究显示携带rs373056577等位基因A的个体发生T2D的风险增加,携带rs121912717 CT基因型的个体甘油三酯水平升高。这项研究的结果需要在更大的队列中进行验证,以获得更可靠的评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Truncated variant rs373056577 confers increased risk of type 2 diabetes and missense variant rs121912717 is associated with hypertriglyceridemia in Bangladeshi population
This study investigates the association of allelic and genotypic variations of rs121912717 and rs373056577 within APOA1 and APOA2 genes, respectively with the risk of type 2 diabetes (T2D). In this cross-sectional study, real-time quantitative PCR with specific Taqman probes was used to determine the genotypic and allelic frequencies of rs121912717 and rs373056577 in 300 unrelated Bangladeshi individuals (Healthy = 144, T2D patients = 156). Logistic regression analysis was performed to investigate the association of genotypic and allelic frequencies of these SNPs with respect to T2D under different inheritance models. Neither allelic nor genotypic frequencies of rs121912717 within APOA1 showed any significant association with T2D. Genotypes with respect to rs373056577 within APOA2 showed significant association with the risk of T2D under co-dominant heterozygous model (GG vs GA) [OR (95 %CI): 2.64 (1.32–5.59), p = 0.008], dominant [OR (95 %CI): 2.31 (1.24–4.49), p = 0.01] and over-dominant [OR (95 %CI): 2.62 (1.31–5.53), p = 0.008] models without adjusting for age, gender and BMI. After adjusting for age, gender and BMI, the A allele of rs373056577 showed significant association with T2D only in the dominant model [OR (95 %CI): 3.20 (1.12–10.51), p = 0.04]. Also, A allele of rs373056577 demonstrated significant association with the risk of T2D compared to allele G with [OR (95 %CI): 2.90 (1.15–8.14), p = 0.03] and without adjusting for confounders [OR (95 %CI): 1.97 (1.14–3.52), p = 0.02]. The genotypic frequency was significantly associated with T2D in codominant, dominant, and overdominant models in male participants when a gender-stratified analysis was conducted for rs373056577. However, when the logistic regression analysis was adjusted for age and BMI, the association was not significant in any of the models with respect to rs373056577 for male participants. On the other hand, gender-stratified regression analyses revealed no significant association with T2D before and after adjusting for age and BMI with respect to both allelic and genotypic frequencies of rs121912717. Individuals with CT genotype of rs121912717 had significantly higher triglyceride levels (322.2 mg/dL) compared to those harboring CC genotype (202.8 mg/dL) with or without adjusting for age, gender, BMI and disease status of the study participants. In conclusion, this study revealed that individuals harboring the allele A of rs373056577 possessed an increased risk of developing T2D and individuals having CT genotype of rs121912717 had increased triglyceride levels. The result of this study needs to be validated in a larger cohort for a more robust assessment.
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来源期刊
Metabolism open
Metabolism open Agricultural and Biological Sciences (General), Endocrinology, Endocrinology, Diabetes and Metabolism
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