Preproghrelin gene polymorphisms in obese Japanese: Association with diabetes mellitus in men and with metabolic syndrome parameters in women.

Preproghrelin gene polymorphisms (SNPs) are possible predisposing factors to obesity and metabolic syndrome. We analysed SNPs in obese Japanese individuals and studied the correlation with diabetes and metabolic syndrome. We recruited 235 subjects (BMI > 28.3) from individuals undergoing periodic medical check-up at Saku Central Hospital. Their SNPs were genotyped using PCR-RFLP method. Frequencies of 5 SNPs in the preproghrelin gene -1500C>G (rs3755777), -1062G>C (rs26311), -994C>T (rs26312), Leu72Met (+408C>A) (rs696217), and +3056T>C (rs2075356) were compared with healthy individuals (data from HapMap Project or Asian population studies). Associations between these SNPs and clinical parameters were investigated. The phenotypes evidently differed between men and women. In men, higher fasting glucose and HbA1c values were observed in the +3056C/C minor homozygotes without leptin or insulin accumulation. The +408C -- +3056C haplotype was more frequent in the diabetic subgroup, in which diagnosis was based on fasting glucose, 75gOGTT, and HbA1c values, than normal subgroup. In contrast, in women, a significant correlation was observed between fat metabolism and obesity. The -1062C/C minor homozygotes had higher values of C-peptide, insulin, total and visceral fat area, waist circumference and BMI. The 72Met/Met minor homozygotes showed reduced leptin, total, HDL and LDL cholesterol concentrations and increased value of visceral fat area. Further, in the other SNPs, the minor homozygotes showed a similar trend, and the heterozygotes had intermediate values. Preproghrelin gene polymorphisms in obese Japanese may be predisposing factors to diabetes mellitus in men and to obesity via aberrant fat metabolism in women.: