Investigation of inflammation related gene polymorphism of the mannose-binding lectin 2 in schizophrenia and bipolar disorder

Objectives:To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).Methods:One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.Results:The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).Conclusion:The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

Schizophrenia (SCZ) and bipolar disorder (BD) are chronic psychiatric disorders that cause substantial disruptions in psychosocial capacity and occur in approximately 1% of the world population.¹ Genome-wide association studies (GWAS) of Psychiatric Genomics Consortium for SCZ recognized more than a hundred common single nucleotide polymorphisms (SNPs) with minor individual effects presenting susceptibility to the SCZ.² A similar mega-analysis for BD, although including a more moderate sample, identified common risk variants specific to BD.³ The long-lasting alterations in gene expression patterns after environmental exposures imply that epigenetic mechanisms might also play a critical role in chronic psychiatric disorders.⁴ Again, previous researches have constantly reported shared genetic etiology between SCZ and BD. Researches showing the genetic overlap between SCZ and BD have improved from studying family and twin inheritance to determine genetic correlation and performing polygenic risk score analysis from GWAS data in large case-control samples.⁵ Despite these researches with large sample size, the cause of both disorders is still relatively unknown; recent studies have shown that uncontrolled activity of microglia and excessive inflammatory responses caused by pro-inflammatory cytokines are among the factors that play a role in the development of SCZ and BD based on genetic susceptibility.^1,6 A relationship between SCZ and many autoimmune diseases and an increase in the prevalence of an autoimmune disease occurrence by about 45% have been found. Moreover, infections of embryonic and early childhood periods lead to delays in fetal brain development and excessive synaptic pruning during adolescence, are among the possible risk factors of psychosis.^7,8 Systemic inflammation and central inflammation are thought to be associated with episodes, remission, and prognosis of BD. Neuroendocrine irregularities, neurotransmitter abnormalities, and glial cell dysfunctions cause plastic alterations in the mood-regulating brain areas. The high rate of comorbid autoimmune diseases also supports this claim.⁹Mannose-binding lectin (MBL) has a vital function in the innate immune system by stimulating the complement system’s lectin pathway. Therefore, it is the only collectin that binds to microorganisms, serves as an opsonin, promotes phagocytosis, and stimulates macrophages. MBL2 gene, which consists of 4 exons in the q11.2-q21 region of the long arm of chromosome 10, encoded MBL. Mutation at codon 54 follows in a replacement of glycine to aspartic acid (allele B), and the normal MBL2 allele is defined by allele A.^10-12 In heterozygous mutants, serum MBL decreases almost 10-fold, whereas, in homozygous mutants, the level decreases to an undetectable level. MBL deficiency is the most common immune defect in humans, affecting approximately 5-7% of individuals.¹³ A decrease in serum MBL level can cause recurrent spontaneous miscarriage,¹⁴ premature birth,¹⁵ and exacerbation of chronic diseases such as ischemic heart disease,¹⁶ and severe infections such as sepsis and systemic inflammatory response syndrome (SIRS).¹⁷ Besides, previous studies suggested that MBL plays an essential role in the pathogenesis of autoimmune diseases.^12,18 We believe that this is the first case-control study comparing MBL2 genotype distributions in patients with SCZ or BD according to treatment resistance, clinical characteristics, and scale scores in detail.Aims of the studyWe aimed to examine whether MBL2 codon 54 polymorphism was involved in the etiopathogenesis and treatment response of SCZ and BD compared with healthy controls.