Jafarian Zahra, Saliminejad Kioomars, Kamali Koorosh, Ohadi Mina, Kowsari Ali, Nasehi Leila, Khorram Khorshid Hamid Reza
a Genetic Research Center , University of Social Welfare and Rehabilitation Sciences , Tehran , Iran.
b Reproductive Biotechnology Research Center , Avicenna Research Institute, ACECR , Tehran , Iran.
Neurol Res. 2018 Jan;40(1):41-44. doi: 10.1080/01616412.2017.1390902. Epub 2017 Oct 26.
Late-onset Alzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder. Associations of the glutathione S-transferases (GSTs) polymorphisms with the risk factors for AD have not been definitely confirmed. We investigated the association of GSTM1 and GSTT1 null deletion and GSTP1 313 A/G polymorphisms and the risk of AD in an Iranian population.
The case group consisted of 280 individuals with AD and the control group included 168 age-matched healthy individuals. The genotyping of the GSTP1 polymorphism was determined by PCR-RFLP and the GSTM1 and GSTT1 deletions were done by multiplex PCR method.
The GSTP1 AG genotype was significantly lower (p = 0.005; OR = 0.57, 95% CI: 0.38-0.84) in the patients (41.1%) than the control group (56.5%). The GSTM1 null genotype was significantly higher (p < 0.001) in the patients (40.5%) than the control group (15.8%). The GSTT1 null genotype was significantly higher (p < 0.038) in the patients (31.2%) than the control group (21.5%). The patients homozygous for the GSTM1 and GSTT1 null alleles showed a 3.5 and 1.5-fold increased risk of AD, respectively. There were interaction between GSTP1 AG genotype and absence of APOE e4 allele (p = 0.001), as well as presence of APOE ε4 and GSTM1 null genotype (p < 0.0001).
These findings suggested that GSTM1 and GSTT1 null deletions may be associated with susceptibility to AD and people with APOE e4 and GSTM1 null deletion have a higher increased risk for Late-onset AD in Iranian population.
晚发型阿尔茨海默病（AD）是一种基因异质性神经退行性疾病。谷胱甘肽S-转移酶（GSTs）基因多态性与AD危险因素之间的关联尚未得到明确证实。我们在伊朗人群中研究了GSTM1和GSTT1无效缺失以及GSTP1 313A/G基因多态性与AD风险的关系。
病例组由280例AD患者组成，对照组包括168例年龄匹配的健康个体。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法检测GSTP1基因多态性，采用多重PCR法检测GSTM1和GSTT1缺失情况。
患者中GSTP1 AG基因型（41.1%）显著低于对照组（56.5%）（p = 0.005；比值比[OR]=0.57，95%可信区间[CI]：0.38 - 0.84）。患者中GSTM1无效基因型（40.5%）显著高于对照组（15.8%）（p < 0.001）。患者中GSTT1无效基因型（31.2%）显著高于对照组（21.5%）（p < 0.038）。GSTM1和GSTT1无效等位基因纯合的患者患AD的风险分别增加3.5倍和1.5倍。GSTP1 AG基因型与APOE ε4等位基因缺失之间存在相互作用（p = 0.001），以及APOE ε4存在与GSTM1无效基因型之间存在相互作用（p < 0.0001）。
这些发现提示GSTM1和GSTT1无效缺失可能与AD易感性相关，在伊朗人群中，携带APOE ε4和GSTM1无效缺失的个体患晚发型AD的风险更高。
