Dimitrakis Efthimios, Katsarou Martha-Spyridoula, Lagiou Maria, Papastefanopoulou Vasiliki, Spandidos Demetrios A, Tsatsakis Aristidis, Papageorgiou Socratis, Moutsatsou Paraskevi, Antoniou Katerina, Kroupis Christos, Drakoulis Nikolaos
Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece.
Department of Clinical Biochemistry, University General Hospital 'ATTIKON', 12462 Athens, Greece.
Exp Ther Med. 2022 Jul 19;24(3):584. doi: 10.3892/etm.2022.11521. eCollection 2022 Sep.
Vitamin D receptor () gene single nucleotide polymorphisms (SNPs) have been investigated over the past years with the aim of identifying any association with the development of Alzheimer's disease (AD). However, information regarding the potential association of SNP haplotypes with AD is limited. The aim of the present study was to provide additional knowledge on the effects of haplotypes on the development of late-onset AD in a cohort of Southeastern European Caucasians (SECs). The study sample included 78 patients with late-onset AD and 103 healthy subjects as the control group. SNPs that were analyzed were TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570). The CAC (TaqI, BsmI and FokI) haplotype was found to be associated with a 53% lower risk of developing the disease (OR, 0.47; 95% CI, 0.23-0.96; P=0.04) and the TAC (TaqI, BsmI and FokI) haplotype was associated with an ~6-fold greater risk of developing AD (OR, 6.19; 95% CI, 1.91-20.13; P=0.0028). Female subjects carrying the TAC haplotype had a ~9-fold greater risk of developing AD in comparison to female control subjects (OR, 9.27; 95% CI, 1.86-46.28; P<0.05). The TaqI and BsmI polymorphisms were in high linkage disequilibrium (D'=0.9717, r=0.8467) and produced a haplotype with a statistically significant different frequency between the control and AD group. The TA (TaqI and BsmI) haplotype was associated with an ~8-fold greater risk of developing AD (OR, 8.27; 95% CI, 2.70-25.28; P<0.05). Female TA carriers had an ~14-fold greater risk of developing the disease in comparison to female control subjects (OR, 13.93; 95% CI, 2.95-65.87; P<0.05). On the whole, the present study demonstrates that in the SEC population, TAC and TA are risk haplotypes for AD, while the CAC haplotype may act protectively. SEC women carrying the TAC or TA haplotype are at a greater risk of developing AD, thus suggesting that women are markedly affected by the poor utilization of vitamin D induced by the haplotype.
在过去几年中，人们对维生素D受体（）基因单核苷酸多态性（SNP）进行了研究，目的是确定其与阿尔茨海默病（AD）发病之间的任何关联。然而，关于SNP单倍型与AD潜在关联的信息有限。本研究的目的是在一组东南欧高加索人（SEC）队列中，提供关于单倍型对晚发性AD发病影响的更多知识。研究样本包括78例晚发性AD患者和103名健康受试者作为对照组。分析的SNP包括TaqI（rs731236）、BsmI（rs1544410）和FokI（rs2228570）。发现CAC（TaqI、BsmI和FokI）单倍型与发病风险降低53%相关（比值比，0.47；95%可信区间，0.23 - 0.96；P = 0.04），而TAC（TaqI、BsmI和FokI）单倍型与患AD的风险高约6倍相关（比值比，6.19；95%可信区间，1.91 - 20.13；P = 0.0028）。携带TAC单倍型的女性受试者患AD的风险比女性对照受试者高约9倍（比值比，9.27；95%可信区间，1.86 - 46.28；P < 0.05）。TaqI和BsmI多态性处于高度连锁不平衡状态（D' = 0.9717，r = 0.8467），并且产生了一种在对照组和AD组之间频率有统计学显著差异的单倍型。TA（TaqI和BsmI）单倍型与患AD的风险高约8倍相关（比值比，8.27；95%可信区间，2.70 - 25.28；P < 0.05）。与女性对照受试者相比，携带TA单倍型的女性患该病的风险高约14倍（比值比，13.93；95%可信区间，2.95 - 65.87；P < 0.05）。总体而言，本研究表明，在SEC人群中，TAC和TA是AD的风险单倍型，而CAC单倍型可能起保护作用。携带TAC或TA单倍型的SEC女性患AD的风险更高，因此表明女性受该单倍型诱导的维生素D利用不良的影响更为明显。
