Review Article

Ghrelin in Diabetes and Metabolic Syndrome

Table 2

Associations of polymorphisms in the GHRL gene.

SNPRisk alleleAssociationSubjectsReferences

Leu72MetMet72Lower age of onset of self-reported obesity96 obese and 96 normal-weight Swedish women[72]

Leu72MetMet72Higher frequency in Whites than in Blackslower BMI, fat mass, visceral fat, total TG and RQ; higher IGF-1 levels in Blacks784 French-Canadian subjects (Quebec Family Study) 778 subjects (276 Blacks and 502 Whites; HERITAGE Family Study) [73]
Arg51GlnGln51Not observed among Blacks1442 subjects (741 from obese registry, 701 from normal reference population; SOS)

Leu72MetMet72Higher BMI, earlier age of onset of obesity and reduced first phase insulin secretion70 tall and obese children[74]

Gln90LeuGln90Higher frequency in obese children, but also in underweight students215 extremely obese German children and adolescents, 93 normal-weight students,134 underweight students, 44 normal-weight adults[75]

Leu72MetMet72Lower serum creatinine and lipoprotein a levels258 Finnish Caucasians with T2D and 522 controls[76]

Arg51GlnGln51Risk allele for hypertension and T2D; predictor of 2-h plasma glucose in OGTT; lower IGF-1 and higher IGFBP-1 concentrations in normotensives; lower AUC insulin519 hypertensive and 526 normotensive Finnish Caucasians[77]

Leu72MetMet72In obese/overweight: higher neonatal weight-for-age; earlier age at onset of obesity; higher IGF-1 concentration.81 obese or overweight and 96 normal-weight Italian children and adolescents and 72 normal-weight young adults[6]

4427G > AGDiffuse large cell lymphoma684 healthy controls and 308 North American subjects with non-Hodgkin Lymphoma[78]

Arg51GlnGln51Lower MetS frequencyHigher fasting glucose,TG, and frequency of MetS and lower HDL cholesterol856 Old Order Amish from US [79]
Leu72MetMet72

Leu72MetMet72More depressed and anxious in patients with methamphetamine dependence. No association with methamphetamine dependence118 Koreans with methamphetamine dependence, 144 controls[80]

Leu72MetNo association with obesity222 obese Korean children[81]

1 5 0 0 C > G
1 0 6 2 G > C
9 9 4 C > T
Leu72Met
CLower HDL cholesterol
All four SNPs: no association with T2D
760 T2D and 641 nondiabetic Koreans [82]

Leu72MetLeu72Higher TG, fasting insulin and HOMA-IR. Higher fasting insulin and HOMA-IR1420 Caucasians (500 normal weight and 920 overweight/obese) [83]
6 0 4 > C/TC

Leu72MetMet72Lower allele frequency in diabetic nephropathy with renal dysfunction. Lower total cholesterol levels in patients with diabetic nephropathy with renal dysfunction138 subjects with diabetic nephropathy, 69 diabetics without nephropathy[84]

Leu72MetMet72Lower creatinine levels in diabetic group. No association with T2D206 T2D, 80 controls[28]

5 0 1 A > CAHigher BMI1045 Finnish subjects from the Oulu Project Elucidating Risk for Atherosclerosis (OPERA) study[85]

Leu72MetNo association with weight loss771 obese Caucasian Europeans[86]

Leu72MetMet72Higher allele frequency in higher BMI group than in normal-weight group. Higher BMI, waist circumference, and change in body weight from age 182238 middle-aged and older Japanese people[87]
Leu72MetMet72Lower BMI in CAD patients but no association with CAD, no association with hypertension, T2D, or dyslipidaemia317 Chinese CAD patients, 323 controls[88]

Leu72MetMet72Higher scores on Drive for Thinness-Body Dissatisfaction subscale264 Japanese women [89]
3056 T > 𝐶 CHigher weight, BMI, fat mass, waist circumference, sum of skinfold thicknesses, self-reported past min and max BMIs and lower HDL chol

Arg51Gln
Leu72Met
Gln51 Higher cholesterol levels over time. Subjects with Gln51and /or Met72 lost body weight faster than patients with Arg51/Leu72210 hemodialysed patients prospectively followed up to 15 months[90]

Leu72MetMet72Persons with 72Met allele have lower risk to develop T2DM507 persons with IGT: the Finnish diabetes prevention study[91]

6 0 4 G/AGPersons with the most common genotype combination of the SNPs 604G/-501A/, Leu72/GLN90 have significantly lower systolic and diastolic blood pressure at baseline and during the 3-year follow-up507 persons with IGT: the Finnish diabetes prevention study [92]
5 0 1 A/CA
Leu72MetLeu72
GLN90LeuGLN90