LINKAGE OF DOPAMINE RECEPTOR D2 (DRD2) MARKERS WITH ESSENTIAL HYPERTENSION IN SINGAPOREAN CHINESE SUBJECTS

In the National University of Singapore Genetics of Hypertension (NUSIGHT) Study, we compared allele and genotype frequencies of three dopamine receptor D2 (DRD2) gene markers in Chinese hypertensive sibling-pairs and unrelated Chinese servicemen to test the hypothesis that the markers are associated with essential hypertension. Essential hypertension is a complex multifactorial disease caused by the interaction of genetic and behavioural factors. Several candidate predisposing genes have been proposed, including those in the dopaminergic neurotransmission pathway. We selected 62 ethnic Chinese non-obese, non-diabetic sibling-pairs on blood pressure > 150/90 mmHg or 24-hour ambulatory blood pressure > 140/90 mmHg, and disease onset < 60 years. We enrolled 176 unrelated ethnic Chinese men as population controls. Two polymorphisms in the coding region (Ser311Cys and NcoI) and one in the 3'UTR (TaqIA) of DRD2 were genotyped. Sib-pair linkage analysis of alleles identical by state and case-control linkage dysequilibrium analysis of allele, genotype and haplotype frequencies were performed. Significantly increased sharing of the marker TaqIA (pZ < 0.004), but not NcoI and Ser311Cys, was observed. However, no association between the three polymorphisms and hypertension was detected. The results suggest that linkage exists between DRD2 and essential hypertension in Singaporean Chinese, hence justifying further and larger genetic studies of this locus.