Fig. 1Linkage disequilibrium analyses of ghrelin single-nucleotide polymorphisms (SNPs; rs2075356, rs696217, rs27647, rs3755777) and a growth hormone secretagogue receptor (GHSR) SNP (rs509030 GC). The strength of the linkage is indicated by the value of D′, and the maximum value (absolute linkage) is 100%. The GHSR SNP had the least linkage with the other ghrelin SNPs.
Table 1The Selected Ghrelin and Growth Hormone Secretagogue Receptor SNPs: Chromosome, Band, and Locus and Polymorphism Type and Class
SNP |
CHR |
Cytogenic band |
CHR locus |
Gene site |
SNP type |
rs2075356 CT (+3056 TC) |
3 |
3p25.3b |
10328809 |
Intron |
Transition substitution |
rs696217 GT (Leu72Met) |
3 |
3p25.3b |
10331457 |
Intron |
Transversion substitution |
rs27647 CT (–604 GA) |
3 |
3p25.3b |
10332468 |
Intron |
Transition substitution |
rs3755777 CG (–1500 CG) |
3 |
3p25.3b |
10333364 |
Intron |
Transversion substitution |
rs509030 GC |
3 |
3q26.31 |
6693674 |
Unknown |
Transversion substitution |
Table 2Hardy-Weinberg Equilibrium, MAF, and Prevalence of Rare Genotypes of the Ghrelin and Growth Hormone Secretagogue Receptor SNPs among T2DM and Non-diabetic Subjects
SNP |
Subjects |
HWE, X2 (all subjects) |
MAF (chi-square test) |
Rare genotype prevalence, % (no./total no.) |
Healthy |
T2DM |
P value |
Healthy |
T2DM |
P valuea
|
rs2075356 CT |
0.56 |
0.096 (18/188) |
0.114 (21/184) |
0.682 |
0.00 (0/94) |
3.3 (3/92) |
0.237 |
rs696217 TG |
0.85 |
0.036 (7/192) |
0.054 (10/186) |
0.573 |
0 (0/96) |
1.08 (1/93) |
0.987 |
rs27647 CT |
1.48 |
0.355 (66/186) |
0.34 (62/182) |
0.860 |
14.0 (13/93) |
14.3 (13/91) |
0.879 |
rs3755777 GC |
3.72 |
0.181 (34/188) |
0.156 (29/186) |
0.613 |
6.4 (6/94) |
3.2 (3/93) |
0.505 |
rs509030 GC |
2.36 |
0.300 (51/170) |
0.317 (57/180) |
0.825 |
11.8 (10/85) |
12.2 (11/90) |
0.889 |
Table 3The Prevalence of Ghrelin and Growth Hormone Secretagogue Receptor SNPs Haplotypes in T2DM and Non-diabetic Subjects
Haplotypes (relatively common ≥3%) |
Haplotype prevalence |
P valuea
|
Non-diabetic (n=85) |
T2DM (n=89) |
GG TT TT GC CG |
5.9 (5) |
0 |
0.062 |
GG TT TT GC CC |
3.5 (3) |
6.7 (6) |
0.539 |
GG TT TT CC CG |
7.1 (6) |
6.7 (6) |
0.828 |
GG TT TT CC CC |
9.4 (8) |
6.7 (6) |
0.712 |
GG TT CT CC CG |
4.7 (4) |
1.1 (1) |
0.337 |
GG CT TT GG CC |
4.7 (4) |
0 |
0.118 |
GG CT TT GC CC |
10.6 (9) |
6.7 (6) |
0.526 |
GG CT TT CC CG |
4.7 (4) |
9 (8) |
0.415 |
GG CT TT CC CC |
11.8 (10) |
14.6 (13) |
0.742 |
GG CT CT GC CC |
4.7 (4) |
0 |
0.118 |
GG CC TT GC CC |
3.5 (3) |
9 (8) |
0.243 |
Total |
11 haplotype |
8 haplotype |
|
Rare haplotypes (<3%) |
|
|
|
Number |
16 |
20 |
Carrier |
29.4 (25) |
39.3 (35) |
Total no. of haplotypes |
27 (11+16) |
28 (8+20) |
0.905 |
Table 4Associations of Ghrelin and Growth Hormone Secretagogue Receptor Polymorphisms with HbA1c: Comparisons between Carriers and Non-Carriers of Minor Alleles and Rare Genotypes of the Examined SNPs
SNP (all study subjects) |
HbA1c, % |
Allele carrier |
Genotype carrier |
Minor |
Non-minor |
P valuea
|
Rare homozygous |
Heterozygous |
Common homozygous |
P valueb
|
rs2075356 CT (3, 33, 150)c
|
6.00 (5.50–7.00) |
6.05 (5.50–8.10) |
0.484 |
6.20 (6.05–7.78) |
5.80 (5.48–7.00) |
6.05 (5.50–8.10) |
0.539 |
rs696217 TG (1, 15, 173) |
5.7 (5.5–8.0) |
6.0 (5.5–8.0) |
0.941 |
- |
- |
- |
- |
rs27647 CT (26, 76, 82) |
6.15 (5.40–8.00) |
6.0 (5.5–7.9) |
0.853 |
6.25 (5.7–8.30) |
5.95 (5.40–7.95) |
6.0 (5.50–7.90) |
0.784 |
rs3755777 GC (9, 45, 133) |
5.90 (5.20–7.90) |
6.20 (5.60–8.03) |
0.207 |
5.40 (4.78–7.93) |
6.00 (5.43–7.80) |
6.20 (5.60–8.03) |
0.202 |
rs509030 GC (21, 66, 88) |
6.00 (5.5–7.75) |
6.20 (5.50–8.10) |
0.488 |
6.20 (5.58–8.80) |
6.00 (5.50–7.30) |
6.20 (5.50–8.10) |
0.431 |
Table 5Associations of Ghrelin and Growth Hormone Secretagogue Receptor Polymorphisms with Insulin Resistance (HOMA): Comparisons between Carriers and Non-Carriers of Minor Alleles and between the Genotypes of the Carriers of the Examined SNPs
SNP (all study subjects) |
HOMA index |
Minor allele |
Genotype carriers |
Carriers |
Non-carrier |
P valuea
|
Rare homozygous |
Heterozygous |
Common homozygous |
P valueb
|
rs2075356 CT (3, 33, 150)c
|
1.70 (1.25–2.75) |
2.10 (1.50–3.50) |
0.132 |
1.40 (1.33–5.30) |
1.70 (1.18–2.73) |
2.1 (1.50–3.50) |
0.319 |
rs696217 TG (1, 15, 173) |
2.4 (1.6–4.2) |
2.0 (1.4–3.4) |
0.517 |
- |
- |
- |
- |
rs27647 CT (26, 76, 82) |
2.2 (1.50–3.60) |
1.80 (1.30–3.00) |
0.165 |
2.25 (1.6–3.1) |
2.15 (1.4–4.15) |
1.8 (1.3–3.0) |
0.369 |
rs3755777 GC (9, 45, 133) |
2.00 (1.20–3.10) |
2.10 (1.50–3.50) |
0.434 |
1.60 (1.10–2.50) |
2.20 (1.20–3.65) |
2.10 (1.50–3.50) |
0.345 |
rs509030 GC (21, 66, 88) |
2.00 (1.50–3.28) |
2.25 (1.40–3.60) |
0.519 |
1.60 (1.38–2.08) |
2.10 (1.50–3.40) |
2.25 (1.40–3.60) |
0.386 |
Table 6Associations of Ghrelin and Growth Hormone Secretagogue Receptor Polymorphisms with Plasma Ghrelin Levels: Comparisons between Carriers and Non-Carriers of Minor Alleles and between the Genotypes of the Carriers of the Examined SNPs
SNP (all study subjects) |
Ghrelin levels, pmol/L |
Minor allele |
Genotype carrier |
Carrier |
Non-carrier |
P valuea
|
Rare homozygous |
Heterozygous |
Common homozygous |
P valueb
|
rs2075356 CT (3, 27, 127)c
|
16.0 (14.2–21.4) |
14.8 (10.2–21.4) |
0.192 |
15.7 (14.8–19.1) |
16.3 (14.0–22.5) |
14.8 (10.2–21.4) |
0.425 |
rs696217 TG (1, 13, 145) |
17.2 (14.2–22.0) |
15.13 (10.9–20.9) |
0.182 |
- |
- |
- |
- |
rs27647 CT (23, 60, 72) |
14.8 (10.7–22.0) |
15.7 (12.2–21.1) |
0.762 |
16.9 (9.9–23.6) |
14.8 (11.7–19.0) |
15.7 (12.2–21.1) |
0.640 |
rs3755777 GC (6, 41, 110) |
15.1 (10.8–19.3) |
15.3 (11.6–22.3) |
0.345 |
12.6 (8.0–19.3) |
15.1 (12.0–19.7) |
15.3 (11.6–22.3) |
0.477 |
rs509030 GC (17, 57, 78) |
15.1 (11.0–20.8) |
15.1 (11.6–21.4) |
0.808 |
14.2 (9.4–21.5) |
15.4 (12.1–20.1) |
15.1 (11.6–21.4) |
0.791 |