Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population

Abstract

BackgroundThe expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.MethodsWe conducted a case–control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP.ResultsOf four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR = 0.46, 95% CI: 0.357-0.59, P < 0.01) and 0.7-fold risk (OR = 0.707, 95% CI: 0.534-0.937, P = 0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR = 0.309, 95% CI: 0.218-0.439 for G allele, P < 0.01), and rs2075572 only in females (OR = 0.399, 95% CI: 0.246-0.648 for G allele, P < 0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR = 0.086, 95% CI: 0.048-0.151, P = 0.01; OR = 0.083, 95% CI: 0.045-0.153, P < 0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR = 0.468, 95% CI: 0.309-0.71, P < 0.01; OR = 0.34, 95% CI: 0.195-0.593, P < 0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P < 0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P < 0.01).ConclusionsThe present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

The Endogenous Opioid System in Schizophrenia and Treatment Resistant Schizophrenia: Increased Plasma Endomorphin 2, and &kappa; and &mu; Opioid Receptors are Associated with Interleukin-6

“…One study reported lowered MOR availability in the brain of SCZ patients who died as a result of suicide, which would be consistent with increased levels of EOS peptides occupying those receptors (Scarr et al, 2012). Our negative findings on β-endorphin levels in SCZ are not in agreement with those of a previous report (Ding et al, 2013). Animal models of SCZ are accompanied by moderate alterations in EOS peptides (Ashok et al, 2019;Schwarzer et al, 2009;Volk et al, 2011;Szűcs et al, 2016;).…”

“…Volk et al found that increased MOR mRNA and protein levels in SCZ are largely independent of illness severity, suggesting that increased MOR expression is part of the disease process rather than a consequence of illness chronicity (Volk et al, 2011). In Han Chinese, a MOR polymorphism may confer risk for SCZ (Ding et al, 2013) while an A118G polymorphism of the MOR gene was associated with SCZ (Šerý et al, 2010). One study reported lowered MOR availability in the brain of SCZ patients who died as a result of suicide, which would be consistent with increased levels of EOS peptides occupying those receptors (Scarr et al, 2012).…”

Systematic analysis of genetic variants in cancer-testis genes identified two novel lung cancer susceptibility loci in Chinese population

“…Previous studies revealed that genetic variants in OPRM1 could modulate the dependence to multiple drugs or chemical agents, including nicotine, cocaine, alcohol [25][26][27]. Due to these properties, OPRM1 has been reported associated with the progression of Alzheimer's disease, Parkinson's disease, Schizophrenia and so on [28][29][30]. In lung cancer, Lennon FE et al found that OPRM1 (also known as MOR) expression was elevated in several human non-small cell lung cancer cell lines.…”

Bioinformatics and Evolution of Vertebrate Nociceptin and Opioid Receptors

“…Most studies have focused on the A118G allele of hMOR, which changes the amino acid Asn to Asp (N40D) in the N-terminus of the hMOR protein (Campa, Gioia, Tomei, Poli, & Barale, 2008;Ding et al, 2013;Dlugos et al, 2011;Gong et al, 2013;Hastie et al, 2012;Hernandez-Avila et al, 2007;Hishimoto et al, 2008;Manini, Jacobs, Vlahov, & Hurd, 2013;Matsunaga et al, 2009;Menon et al, 2012;Olsen et al, 2012;Ray et al, 2011;Weerts et al, 2013). The location of numerous hMOR SNPs to the 5 0 -untranslated region (5 0 UTR) and upstream promoter regions as well as 3 0 UTR regions of hMOR do not affect the receptor structure but do alter the expression of hMOR and may explain individual differences in pain sensitivity, drug dependency, and the clinical efficacy of morphine (Klepstad, Dale, Skorpen, Borchgrevink, & Kaasa, 2005;Mayer & Hollt, 2006;Uhl, Sora, & Wang, 1999).…”