分子病理学知识库

BACKGROUND:

There is ample evidence supporting the idea that mitochondrial dysfunction and altered expression of complex I subunits play important roles in the pathophysiology of mental disorders. Early literature reports have implicated NDUFV2, a nuclear-encoded mitochondrial complex I subunit gene, in bipolar disorder and schizophrenia. There has been no genetic study to investigate whether there is an association between NDUFV2 and major depressive disorder (MDD).

METHODS:

This study recruited 744 patients with MDD and 767 well-matched healthy controls in a Chinese Han population, and genotyped 9 SNPs within NDUFV2.

RESULTS:

Initial analysis showed statistically significant differences for 2 SNPs (rs4798765 and rs12964485) in the genotypic distribution and for 1 SNP (rs4797356) in the allelic distribution between the case and control groups. Nevertheless, no significance was demonstrated following multiple testing corrections. Haplotype analysis showed that the T-C haplotype, consisting of rs12457810 and rs12964485, was significantly associated with MDD (P=0.005, corrected P=0.04 after a 10,000 permutation test). We performed an eQTL analysis and found that rs12964485 was significantly associated with NDUFV2 expression in the occipital cortex (P=0.036), albeit this significance did not survive after Bonferroni correction.

LIMITATION:

This is a preliminary investigation with a relatively modest sample size.

CONCLUSION:

Our findings provided preliminary evidence that a haplotype T-C consisting of rs12457810 and rs12964485 in the 5'-upstream region of NDUFV2 may be a protective factor for the development of MDD in Han Chinese.