Abstract An investigation into the D727E polymorphism in the TSH receptor genein patients with congenital hypothyroidism

*Author for Correspondence.
Department of Molecular Medicine
University of Malaya
50603, Kuala Lumpur, Malaysia

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Abstract.
We had recently detected the germline D727E polymorphism of the thyroid-stimulating receptor (TSHR) gene in a cohort of patients with congenital hypothyroidism (CH). The role of TSHR genetic variants in CH has not been well studied. This study investigated the possible relationship between the polymorphism and CH in these patients. We studied 104 normal subjects as control and 33 patients with CH. A PCR-RFLP analysis was used to identify the mutation. There was no significant difference in either the genotype distribution or allelic frequencies between total CH and total controls for the D727E polymorphism (P=0.248 and 0.222 respectively). The controls and the patients with CH were further subdivided into 3 groups according to their ethnicities: Malay, Chinese and Indian. There were no significant differences in the D727E polymorphism genotype distribution between 1) the Malay patients with CH and the Malay normal healthy controls (P=0.442) 2) the Chinese patients with CH and the Chinese healthy controls (P=0.410) and 3) the Indian patients with CH and the Indian healthy controls (P=0.433). In addition, there were also no significant differences of the frequency of the C allele between 1) the Malay patients with CH and the Malay healthy controls (P=0.251) the Chinese patients with CH and the Chinese healthy controls (P=0.251). However, we found that the C allele for the D727E polymorphism was significantly more common in the Indian patients with CH as compared to the Indian healthy controls (P=0.03). These findings suggest that in this cohort of CH patients, the D727E polymorphism of the TSHR gene is a predisposing genetic factor for the development of CH in the Indian but not in the Malay and Chinese.