The HLA-G Genetic Contribution to Bipolar Disorder: A Trans-Ethnic Replication

• Published in: Immunological investigations 2018-08, Vol.47 (6), p.593-604
• Main Authors: Sundaresh, Aparna, Wu, Ching-Lien, Chinnadurai, Raj Kumar, Rajkumar, Ravi Philip, Mariaselvam, Christina Mary, LeMaoult, Joël, Krishnamoorthy, Rajagopal, Leboyer, Marion, Negi, Vir Singh, Tamouza, Ryad
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Bipolar disorder; Bipolar Disorder - complications; Bipolar Disorder - genetics; Bipolar Disorder - immunology; Case-Control Studies; Ethnic Groups - genetics; expression; Female; France; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; HLA-G; HLA-G Antigens - genetics; HLA-G Antigens - immunology; Humans; immune dysfunctions; INDEL Mutation - genetics; Male; Middle Aged; polymorphism; Polymorphism, Single Nucleotide - genetics; South Indian Tamil population; Toxoplasma; Toxoplasma gondii; Toxoplasmosis - complications; Young Adult
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820139.2018.1469649

Bipolar disorder (BD) is frequently associated with immune dysfunctions. Studying the genetic diversity of the immuno-modulatory human leukocyte antigen (HLA)-G locus in a French BD cohort, we previously reported an association between a functionally relevant 14 bp Ins/Del polymorphism and BD risk. The present study investigated the genetic and expression diversities of HLA-G in a geographically distinct South Indian population-group BD patients, as well as the influence of exposure to the neurotropic Toxoplasma gondii pathogen. Three functionally relevant HLA-G polymorphisms, i.e. HLA-G 14 bp Ins/Del (rs66554220), +3142G>C (rs1063320) and +3187A>G (rs9380142) were genotyped by polymerase chain reaction (PCR) and real-time PCR. Sub-samples of BD patients and healthy controls (HC) were investigated for plasma levels of soluble HLA-G (sHLA-G) isoforms, as well as circulating stigma of T. gondii infection. Findings indicate: (i) the frequency of the HLA-G 14 bp Del/Del genotype was higher in BD cases, as compared to HC; (ii) the HLA-G + 3142 C allele and CC genotype were more prevalent in BD patients than in HC; (iii) sHLA-G levels were significantly higher in BD cases, especially in females and in the early onset sub-group; and (iv) the InsGA haplotype was more prevalent in HC. Our findings further support the genetic contribution of HLA-G to BD risk, as well as indicate relevant expression profiles. Such data may also indicate a potential developmental role in BD etiology, given that HLA-G is an important immune regulator from the intrauterine period and across development.