Objective: Low plasma adiponectin level can predict the development of hypertension after 5 years in our population. We therefore investigated whether single-nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with hypertension. Design and methods: We genotyped 14 tagging SNPs in 1616 subjects with persistent normotensive or hypertensive status during a 6.4-year follow-up period in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2). Plasma adiponectin level was measured in 1385 subjects using in-house sandwich ELISA. Results: The minor G allele of the SNP rs266729 was significantly associated with higher odds of hypertension (odds ratio (95% confidence interval)Z1.49 (1.13-1.95), PZ0.0044) after adjusting for covariates. In stepwise multiple logistic regression, this SNP (PZ0.006) was a significant independent factor of hypertension, together with age (P!0.001), body mass index (P!0.001), triglycerides (PZ0.021), and insulin resistance index (P!0.001). Among the 14 SNPs, rs266729 (bZK0.067, PZ0.0037), K10677COT (bZ0.069, PZ0.0027), rs182052 (bZK0.097, P!0.0001), and rs12495941 (bZ0.103, P!0.0001) were significantly associated with adiponectin level after adjusting for covariates. No significant sex interaction was found for the associations of SNPs with hypertension and adiponectin level. Similar results were obtained in haplotype analysis. Conclusion: In our population, genetic variants in the adiponectin gene influenced plasma adiponectin levels, and one of them was associated with hypertension. This study has provided further evidence for a role of adiponectin in the development of hypertension.