Singh HariOm, Samani Dharmesh, Nambiar Nayana, Ghate Manisha V, Gangakhedkar R R
Department of Molecular Biology, National AIDS Research Institute, Pune, India.
Department of Clinical Sciences, National AIDS Research Institute, Pune, India.
APMIS. 2018 Apr;126(4):329-336. doi: 10.1111/apm.12817.
Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV-associated neurocognitive disorders (HAND). The coding region polymorphism in MMP-21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP-21 polymorphism with the modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. Genotyping of MMP-21 572C/T polymorphism was performed by PCR-RFLP in total 150 HIV-infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP-21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP-21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP-21 572TT genotype underrepresented in HIV-infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP-21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP-21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP-21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV-infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP-21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP-21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.
基质金属蛋白酶（MMPs）对细胞外基质（ECM）的重塑被认为是HIV相关神经认知障碍（HAND）发生发展的一个原因。MMP - 21 572C/T基因的编码区多态性可能对ECM重塑具有潜在的功能影响。因此，我们旨在研究MMP - 21多态性与HAND严重程度的调节及其在HIV感染者和健康个体中的患病率之间的关联。通过PCR - RFLP对总共150名HIV感染者进行MMP - 21 572C/T多态性基因分型，其中50名患有HAND，100名未患HAND，另有150名健康对照。与未患HAND的患者相比，HAND患者中MMP - 21 572TT基因型的比例显著更高（OR = 1.63，p = 0.57）。MMP - 21 572T等位基因与HAND严重程度风险降低相关（OR = 0.50，p = 0.04）。同样，与健康对照相比，HIV感染者中MMP - 21 572TT基因型的比例较低（3.0%对6.7%，OR = 0.27，p = 0.08）。MMP - 21 572CT基因型与HIV疾病早期阶段显示出HIV疾病进展风险较高，具有边缘显著性（OR = 1.89，p = 0.07）。MMP - 21 572CT基因型增加了烟草使用者中HAND严重程度调节的风险（OR = 1.98，p = 0.43）。在烟草和酒精使用者中，MMP - 21 572CT基因型在HIV感染者中显示出HAND发生风险升高（OR = 2.30，p = 0.15；OR = 1.86，p = 0.23）。同样，MMP - 21 572TT基因型增加了烟草使用者中HAND发生的风险（OR = 3.48，p = 0.40）。总之，编码区572T等位基因的存在可能对HAND严重程度具有保护作用。MMP - 21 572C/T多态性以及烟草和酒精使用可能促进HAND的发生。
