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Hepatic lipase (HL) plays a major role in the regulation of plasma lipids. Several groups seeking to find association between the gene encoding HL ( LIPC) and plasma concentrations of high-density lipoprotein cholesterol (HDLc) using various methods and populations have reported conflicting results. We have approached the problem of demonstrating a relationship between the LIPC locus and HDLc by means of haplotype association using four single nucleotide polymorphisms (SNPs) (rs12594375G/A, rs8023503C/T, rs4775047C/T, and rs11634134T/A) located in intron 1 of the LIPC gene in two independent Japanese populations consisting of 2,970 and 1,638 individuals, respectively. Significant association between hyperalphalipoproteinemia and a specific haplotype in this intron was detected in both populations. When HDLc levels among the three haplotypic categories were analyzed [haplotype rs8023503C/rs12594375G (haplotype-1; H1) homozygotes (H1H1), haplotype rs8023503T/rs12594375A (haplotype-2; H2) homozygotes (H2H2), and heterozygotes (H1H2)], HDLc levels were lowest among H1H1 [mean ± standard error (SE) = 58.4 ± 0.4 mg/dl], highest among H2H2 (62.5 ± 0.8 mg/dl), and intermediate among H1H2 (59.2 ± 0.4 mg/dl) ( P = 0.00011), indicating that H2 haplotype elevates plasma HDLc levels. This association was validated in the second population ( n = 1,638) ( P = 0.00070). The results provide convincing evidence that the LIPC locus influences HDL metabolism. [ABSTRACT FROM AUTHOR]

The associations of the C825T polymorphism (rs5443) of the G-protein beta3 subunit (GNB3) gene and eight adjacent single nucleotide polymorphisms (SNPs) with diabetes were examined using a Japanese population (n (M/W): 2956 (1335/1621); age: 63.0+/-10.2 years). Fasting plasma glucose (FPG) levels were significantly associated with the C825T polymorphism and two flanking SNPs (rs2301339 and rs5446) (p=0.002, 0.001, and 0.008, respectively). A case-control association study of the C825T polymorphism with diabetes using multiple logistic regression analysis showed a significant association of the genotypes TT+TC with an odds ratio of 0.62 (p=0.008) independent of age, gender, and BMI. The effects of salt consumption on the association were then examined (n=1635). The FPG levels were significantly associated with the C825T polymorphism only in subjects with low salt consumption (<12.44 g/day) (p=0.002). A case-control association study also showed a significant association with diabetes only in subjects with low salt consumption (p=0.006).