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

ABSTRACT

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.

KEYWORDS:

• Bipolar disorder
• expression
• HLA-G
• immune dysfunctions
• polymorphism
• South Indian Tamil population
• Toxoplasma gondii

Acknowledgments

We record our thanks to the patients with bipolar disorder and the healthy controls who consented to participate in our study.

Disclosure statement

The authors report no conflict of interest

Additional information

Funding

This work was supported by a research grant from the Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA), [Project No. 5103-I]. Aparna Sundaresh gratefully acknowledges the receipt of Intramural Funding for PhD work from Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER).