Figure 2.

Functional variation in the CHGA promoter. A, Promoter haplotypes, each represented by a circle whose area represents the overall frequency of that haplotype in the sample. Each haplotype number corresponds to haplotype numbers in table 2. Each circle is subdivided to show the proportion of the individual haplotype frequency found in each of the four populations as represented by the indicated colors. Dashed lines indicate alternative topologies of equal length. Lines connecting haplotypes represent one nucleotide substitution, except where noted in parentheses. B, Association of CHGA proximal promoter SNP genotype (G-988-T) with in vivo plasma CHGA peptide levels in 102 subjects. All CHGA peptides levels are expressed as mean±SEM. Significant differences could be observed in two peptide fragments (large fragment, CHGA_116–457; and pancreastatin, CHGA_284–301) between minor-allele homozygotes and the other two groups. N = number of subjects for each genotype group. The allele frequencies were 22.5% for G and 77.5% for T. The genotypes were in Hardy-Weinberg equilibrium (χ²=0.011; P=.91). C, In vitro haplotype-specific CHGA promoter activity assay. Two haplotypes (3 and 6) showed a marked decrease in promoter activity compared with the other four common promoter haplotypes, two rare haplotypes, and chimp haplotype. Haplotype numbers correspond to haplotype numbers in table 2. There are also significant differences in promoter activity between haplotypes 3 and 6. *P<.0001 between haplotype 6 and other haplotypes. **P<.001 between haplotype 3 and the other haplotypes except haplotype 6. D, In vitro mutated haplotype activity assay in the CHGA promoter. Each mutated promoter haplotype was derived from either haplotype 1 or haplotype 6 (see table 2).