An Exploratory Case-Control Study for Mitochondrial DNA G10398A in Bipolar I Disorder Patients with a Family History of Affective Disorders.

Abstract

The mitochondrial DNA (mtDNA) G10398A polymorphism has been associated with bipolar disorder (BD). It leads to an amino acid substitution within NADH dehydrogenase subunit, thereby altering the mitochondrial complex I function. This exploratory case-control study assesses the association of mtDNA G10398A with the risk of BD and its relationship to clinical variables in Indian patients. Cases met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of BD-I in remission and had a family history of BD or recurrent unipolar disorder in biological relatives. The healthy controls (HC) had no known illness and were screened negative for Family Interview for Genetic Studies. Participants were assessed using Clinical Pro forma, NIMH-Life Chart Method and Alda lithium response scale. The mtDNA G10398A was assessed with real-time polymerase chain reaction using TaqMan assay. A total of 82 participants were recruited across cases and controls, with 42 patients (50% with maternal history) and 40 healthy individuals with similar demographic profiles. The mean age of onset was 25.16 (standard deviation [SD] 7.6) years, with illness for 11.59 years (SD: 7.18). Allele A was found in 50% of cases compared to 32.5% HC (odds ratio = 2.08; 95% confidence interval [CI]: 0.85-5.09). Findings remain non-significant for patients with maternal mood disorders (allele A: 38.9%; 21/42). Cases with allele G had significantly higher body mass index (BMI) (P = 0.008) than those with allele A. The study adds information on mtDNA 10398A amongst Indian patient samples and healthy individuals. No significant group difference was found with respect to mtDNA G10398A. The positive association of allele G with higher BMI has potential clinical relevance that can be further investigated in larger samples.