Association of MME gene polymorphisms with susceptibility to Alzheimer's ' s disease in an Iranian population

Background: the MME gene encodes a membrane metalloendopeptidase, known as neprilysin (NEP). There are no reports on the potential implications of MME gene polymorphisms on the risk of Alzheimer's disease (AD) in the Iranian population. In this study, we studied the potential association of two single nucleotide polymorphisms (SNPs), rs6797911 and rs3736187, in the MME gene and the risk of developing AD in an Iranian population. Methods: This case-control study comprised 120 AD-diagnosed patients and 120 healthy individuals without any prior family history of AD. The patient and control groups were matched for major demographic and health characteristics. Genotyping was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results: All patients included in this study were assessed by an experienced neurologist to exclude cases with other forms of dementia based on a brain computed tomography scan and other clinical findings. There were no significant differences in demographic and health characteristics including sex, diabetes, blood pressure, and cigarette smoking status between case and control groups (p > 0.05). However, the age difference appeared significant. Both SNPs were significantly associated with the risk of AD in our study population. The rs3736187 (T > C, 3:155168489) was strongly associated with AD risk under the log-additive model (OR = 1.67, CI = 1.18-2.37, pvalue = 0.003). The rs6797911 (T > A, 3:155144601) also showed a significant association with AD risk under the dominant model (TT vs. TA and AA, OR = 3.37, CI = 1.86-6.1, p-value <0.001). Conclusion: There is a strong association between MME gene polymorphisms and susceptibility to AD in the Iranian population. Amyloid-beta (A beta) can serve as a substrate for the NEP metalloendopeptidase, the product of the MME gene. However, the mechanistic understanding of how these genetic variations affect NEP expression, function, and consequently susceptibility to AD, is poorly understood. Further research is required to fully understand the exact implication of MME gene variations on AD, particularly in a larger, ethnicity-diverse population.