New alterations at potentially regulated regions of the Glial Derived Neurotrophic Factor gene in bipolar disorder

Introduction: Glial Derived Neurotrophic Factor (GDNF) plays an important role in the survival and differentiation of neurons. We examined 5'upstream and 3' untranslated region of the GDNF gene by PCR amplification and direct sequencing to explore the effect of alteration in the potentially regulated part of GDNF in bipolar disorder.

Materials and methods: Sixty-six patients with bipolar disorder, 27 first degree relatives of these patients and 56 healthy volunteers were screened for mutations and polymorphisms in GDNF gene.

Results: Seven previously reported polymorphisms and additional three novel allele variants of GDNF were detected. Association test of rs2075680 C>A SNP showed significant difference between patients and healthy subjects with higher allele frequency in healthy subjects performing Chi-square test. However, there was no significant difference after multiple test corrections between groups. There were no significant differences in association test of rs2075680 C>A SNP between first degree relatives and healthy volunteers/patients. rs142426358 T>C SNP was seen only in one patient with an early age of illness onset. New T>A alterations were found in chromosome locations 5:37812784 and 5:37812782 in two male bipolar disorder patients with age of illness onset 12 and 24 years.

Limitations: The sample size was relatively small.

Discussion: Our study proposes the suggestive association between polymorphisms in the potential regulatory sites of GDNF and bipolar disorder.