Ghrelin Gene Variants Influence on Metabolic Syndrome Components in Aged Spanish Population.

BACKGROUND: The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people. OBJECTIVES: We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components. SUBJECTS AND METHODS: 824 subjects (413 men/411 women, age 77.31±5.04) participating in the Mataró aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%. RESULTS: No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of -604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters. CONCLUSION: Ghrelin gene variants -604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects.

Aging phenotype and its relationship with IGF-I gene promoter polymorphisms in elderly people living in Catalonia.

OBJECTIVES: Genetic variations in the Insulin/IGF-I genes pathway have been related to longevity, dementia, metabolic diseases and cancer. The purpose of the present study was to investigate the 192 bp allele of IGF-I gene promoter and its relationship with metabolic syndrome (MS) components, mental and nutritional state, muscle strength and functional capacity in an aged Spanish population. DESIGN: Population-based study (Mataró Ageing Study), including 292 subjects (144 men and 148 women, mean age 77.0±5.4). Anthropometric variables, lipid profile, glucose and blood pressure (BP) were measured; mental state (MMSE), nutritional state (MNA) and Barthel scale were performed, and were correlated to the presence of the 192 bp allele of IGF-1 gene promoter polymorphisms. RESULTS: MS (ATP-III criteria) was found in 49.5% (41.4% in men and 57.6% in women). The 192 bp allele of IGF-I gene promoter was distributed as: 41.9% homozygous, 44.3% heterozygous and 13.9% were non-carriers of this allele. A lower prevalence of metabolic syndrome was observed in homozygous (41.9% vs 54.9% in heterozygous+non-carriers, p=0.031). Mental state (MMSE), nutritional state (MNA) and Barthel scale were better in homozygous individuals compared to heterozygous and non-carriers (p=0.015, p=0.026 and 0.047, respectively). In men, MNA was better in homozygous with no differences in MMSE and Barthel scales. In homozygous women, BP was lower (p=0.009) and Barthel scale was better (p=0.05) with no differences in MMSE and MNA. CONCLUSION: Homozygosity for the 192 bp allele of the IGF-I gene polymorphism suggests a healthier aging condition, with less prevalence of cardiometabolic disturbances, and better mental, nutritional and functional state.

Relationship between ghrelin and the metabolic syndrome in the elderly: a longitudinal population-based study.

CONTEXT: Ghrelin regulates energy homeostasis and may contribute to the development of the metabolic syndrome (MS) in the elderly. OBJECTIVE: To study the relationship between ghrelin and the MS, IGF-I and life style factors over a 2-year follow-up. DESIGN: Longitudinal population-based study, starting from 2002; 2 years follow-up. PARTICIPANTS: Three hundred and thirteen (153 men/160 women) individuals living independently older than 70 years. RESULTS: MS was found in 54.9% of men and 61% of women. In the 229 subjects available at follow-up, ghrelin was higher in men than in women at basal (P = 0.002) and 2-year follow-up (P = 0.004). Ghrelin decreased over time in both genders (P < 0.01). Ghrelin was lower in individuals showing MS compared to non-MS (P = 0.08), but this difference was more evident at 2-year follow-up (P = 0.016), mostly due to men with MS (P = 0.002) and even after adjustment for BMI, gender and age. Individuals with MS had an OR of 1.67 (95% CI: 1.0-2.78) for low ghrelin (< first tertile); when adjusting by BMI, gender and age, only high triglycerides with OR 1.8 (1.0-3.3), remained statistically significant among the MS components. IGF-I showed a positive correlation with ghrelin only in individuals without MS (r(s) 0.403, P < 0.001) with no gender differences; this relationship was not found in MS (r(s) 0.120, P = 0.129). A positive association of ghrelin was found with academic level, alcohol consumption and smoking. CONCLUSIONS: Ghrelin is higher in old men in comparison to women and decreases over time with a steeper decline in subjects with MS; moreover, in these subjects ghrelin/IGF-I correlation is lost.