Sayed Shomoita, Saba Abdullah Al, Hasan Imrul, Rahat Rafia, Sayem Mohammad, Ebihara Akio, Nabi A H M Nurun
Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, 1000, Bangladesh.
United Graduate School of Agricultural Science, Gifu University, 1-1 Yanagido, Gifu Shi, 501-1193, Japan.
Metabol Open. 2025 Apr 14;26:100364. doi: 10.1016/j.metop.2025.100364. eCollection 2025 Jun.
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.
本研究分别调查了载脂蛋白A1（APOA1）基因中的rs121912717以及载脂蛋白A2（APOA2）基因中的rs373056577的等位基因和基因型变异与2型糖尿病（T2D）风险之间的关联。在这项横断面研究中，采用带有特异性Taqman探针的实时定量PCR来测定300名无亲缘关系的孟加拉人个体（健康者 = 144名，T2D患者 = 156名）中rs121912717和rs373056577的基因型和等位基因频率。进行逻辑回归分析，以研究在不同遗传模型下这些单核苷酸多态性（SNP）的基因型和等位基因频率与T2D的关联。APOA1基因中的rs121912717的等位基因频率和基因型频率均未显示与T2D有任何显著关联。APOA2基因中的rs373056577的基因型在共显性杂合模型（GG与GA）下与T2D风险存在显著关联[比值比（95%置信区间）：2.64（1.32 - 5.59），p = 0.008]，在显性模型[比值比（95%置信区间）：2.31（1.24 - 4.49），p = 0.01]和超显性模型[比值比（95%置信区间）：2.62（1.31 - 5.53），p = 0.008]下，未对年龄、性别和体重指数（BMI）进行校正。在对年龄、性别和BMI进行校正后，rs373056577的A等位基因仅在显性模型下与T2D存在显著关联[比值比（95%置信区间）：3.20（1.12 - 10.51），p = 0.04]。此外，与G等位基因相比，rs373056577的A等位基因在未校正混杂因素[比值比（95%置信区间）：1.97（1.14 - 3.52），p = 0.02]以及校正后[比值比（95%置信区间）：2.90（1.15 - 8.14），p = 0.03]均显示与T2D风险存在显著关联。当对rs373056577进行性别分层分析时发现，在男性参与者中，基因型频率在共显性、显性和超显性模型下均与T2D存在显著关联。然而，当对逻辑回归分析校正年龄和BMI后，对于男性参与者，rs373056577在任何模型中均无显著关联。另一方面，性别分层回归分析显示，无论是否校正年龄和BMI，rs121912717的等位基因频率和基因型频率与T2D均无显著关联。无论是否校正研究参与者的年龄、性别、BMI和疾病状态，rs121912717的CT基因型个体的甘油三酯水平（322.2毫克/分升）均显著高于CC基因型个体（202.8毫克/分升）。总之，本研究表明，携带rs373056577的A等位基因的个体患T2D的风险增加，而具有rs121912717的CT基因型的个体甘油三酯水平升高。本研究结果需要在更大的队列中进行验证，以进行更可靠的评估。
