|(T;T)||3||reduced abilities related to neurocognition and ability to recognize faces|
Rs2237717 (major: C, minor: T) is located in intron 11 within the MET proto-oncogene. The MET gene is primarily known to be involved in tumor metastasis [PMID 18175071]. However, MET has also been shown to have roles in general neurodevelopment [PMID 12397180] and in the development of autism [PMID 19360663]. Rs2237717 has been linked to schizophrenia, ability to recognize facial emotion, and chronic rhinosinusitis.
Association with schizophrenia and cognitive ability
Given that schizophrenic patients have a lower incidence of cancer despite more exposure to risk factors and relatives without schizophrenia appear to also have a protective effect on cancer incidence, it has been hypothesized that alterations in cancer genes (like MET, containing rs2237717) may be involved in the pathogenesis of schizophrenia [PMID 18331573].
In a study by Burdick et al [PMID 20080979] which investigated the relation between SNPs in MET gene and schizophrenia, it was found that rs2237717 resided in an enriched haplotype of one of the four haplotype blocks. The ‘Block 3’ haplotype was the most commonly underrepresented in the schizophrenia case group (p = 2.5e-4, OR = 0.40, 95% CI = 0.24—0.65). Rs2237717 was one of three SNPs in the haplotype block to survive correction with permutation (p = 0.002), with 37.9% of the cases and 49.6% of the controls showing the ancestral allele (C). The ancestral allele is thus considered a protective allele against schizophrenia. This test was replicated by the authors using a dominant model and the results remained significant (p = 0.001). These results represent the first report of an association between MET and schizophrenia and the second of an association of MET with susceptibility to neuropsychiatric illness (autism, [PMID 19360663].
General cognitive ability
They also reported that the MET haplotype which was inversely correlated with schizophrenia (‘Block 3’ containing rs2237717) had a significant impact on neurocognition. Carriers of the major allele at rs2237717 in the comparison group performed significantly better than non-carriers on a test of general cognitive ability.
Association with facial emotional perception
Another study by Lin et al [PMID 22558359] showed the rs2237717 SNP is associated with facial emotional perception. The CT and CC genotypes enhanced facial emotional perception as compared to those with the TT genotype (ANOVA p = 0.016 and GLM p = 0.018, controlled for age, gender, and education). There was also an interaction of rs2237717 with rs1130233 in the AKT gene in the same signaling pathway, in which the rs2237717 C carrier/ rs1130233 G carrier group showed better facial emotional perception than those with the TT/AA genotype (ANOVA p = 0.035 and GLM p = 0.015), controlled for neurocognitive functions. According to the authors, this is the first study to suggest that genetic factors can affect performance of facial emotion perception.
Association with chronic rhinosinusitis
The MET gene has been implicated in nasal polyp development [PMID 19532090], and Castano et al [PMID 20416453] showed that the minor allele at rs2237717 is associated with chronic rhinosinusitis in patients with nasal polyps (genotypic P nominal = 0.09, empirical P = 0.04, OR = 1.4, CI = 1.0-1.9). This suggests that polymorphisms in the MET gene, including rs2237717, may play a role in the susceptibility to develop CRS. Study findings apply to patients with nasal polyps and severe CRS unresponsive to surgery.
[PMID 20080979] Association of genetic variation in the MET proto-oncogene with schizophrenia and general cognitive ability
[PMID 22558359] MET and AKT Genetic Influence on Facial Emotion Perception
[PMID 20416453] c-MET pathway involvement in chronic rhinosinusitis: a genetic association analysis
[PMID 19002214] MET and autism susceptibility: family and case-control studies.