Relationship between the LHPP Gene Polymorphism and Resting-State Brain Activity in Major Depressive Disorder

Abstract

A single-nucleotide polymorphism at the LHPP gene (rs35936514) has been reported in genome-wide association studies to be associated with major depressive disorder (MDD). However, the neural system effects of rs35936514 that mediate the association are unknown. The present work explores whether the LHPP rs35936514 polymorphism moderates brain regional activity in MDD. A total of 160 subjects were studied: a CC group homozygous for the C allele (23 individuals with MDD and 57 controls) and a T-carrier group carrying the high risk T allele (CT/TT genotypes; 22 MDD and 58 controls). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Brain activity was assessed using the amplitudes of low-frequency fluctuations (ALFF). MDD patients showed a significant increased ALFF in the left middle temporal gyrus and occipital cortex. The T-carrier group showed increased ALFF in the left superior temporal gyrus. Significant diagnosis × genotype interaction was noted in the bilateral lingual gyri, bilateral dorsal lateral prefrontal cortex (dlPFC), and left medial prefrontal cortex (mPFC) (P < 0.05, corrected). Results demonstrated that MDD patients with LHPP rs35936514 CT/TT genotype may influence the regional brain activity. These findings implicate the effects of the rs35936514 variation on the neural system in MDD.

LHPP suppresses bladder cancer cell proliferation and growth via inactivating AKT/p65 signaling pathway

“…It is ubiquitously expressed in brain, kidney, liver and urinary bladder tissues [13]. A genome-wide association study has revealed a single-nucleotide polymorphism (SNP) at the LHPP gene (rs35936514) correlated with major depressive disorder [6]. Recently, the involvement of LHPP in cancer development has been discovered.…”

“…Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is conserved from worm to human with a 28% identity [5]. It is originally discovered in swine brain tissue [6,7]. Recently, LHPP has been identified as a tumor suppressor gene in hepatocellular carcinoma (HCC) by targeting PI3K/AKT signaling pathway.…”

LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

“…Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) was first detected in swine brain tissue. [5,6]. Protein phosphorylation plays an important role in epigenetics, which is considered to be a powerful means of regulating carcinogenic activity [7,8].…”

Neuroimaging genomic studies in major depressive disorder: A systematic review

“…Associations between APOE ε4 and ACE genes and functional connectivity of a default‐mode network have also been reported . An association between the DAOA gene and activity was found in left uvula of cerebellum and left middle temporal gyrus among people with MDD, and significant LHPP genotype‐diagnosis effects existed in the bilateral dorsal lateral frontal cortex and left medial prefrontal gyrus in another study …”