English abstract
Adiponectin (Acrp30), an adipocyte-secreted protein encoded by the apMl gene, is known to modulate insulin sensitivity and glucose homeostasis. Plasma adiponectin levels correlate well with insulin sensitivity, and are decreased in type 2 diabetes, obesity and hypertension. The gene is located on chromosome 3,27 and it is linked to type 2 diabetes. To identify the genetic variations of the apMl gene that contribute to the development of obesity, insulin resistance, dyslipidemia and hypertension, we screened 100 Omani Arab individuals for single-nucleotide polymorphisms (SNPs) in a 517 bp fragment in the promoter region of adiponectin gene: two common SNPS were detected (SNP-11391GA and SNP-11377CG) and one rare SNP-11043CT. We were able to detect a new rare SNP-11055AC in one of the individuals. The two frequent SNP-11391 and SNP-11377 were further genotyped in 230 individuals. We found that individuals carrying the CG and GG genotype at SNP-11377 to be associated significantly with higher BMI (P=0.001), total body fat percent (P-0.000), waist circumference (P-0.001), waist to hip ratio (P=0.031), systolic blood pressure (P-0.003) and hypertension (P=0.032). While the CC genotype individuals at SNP-11377 were significantly associated with higher insulin resistance (P-0.000) and a trend of association with lower HDL cholesterol (P-0.073). On the other hand, we failed to detect any association between SNP-11391GA and any components of the metabolic syndrome. However, the A allele at SNP-11391 was associated with higher diastolic blood pressure (P-0.051). Furthermore, no association was detected between SNP-11377CG with metabolic syndrome defined by both WHO and NCEPP. This might be due to the difference in the risk allele associated with various components of the metabolic syndrome. We also carried out association tests between adiponectin SNPs with growth hormone, leptin and thyroid function. No association was detected between SNP-11391 or SNP-11377 with leptin and growth hormone. However, there was significant association between SNP. 11377 with higher thyroxin hormone levels and a trend of association between SNP11391 and lower thyroid stimulating hormone. All calculations were adjusted for age, sex and BMI TDT analyses of the pedigree showed significant association between SNP-11377 and BMI [P=0.0003], waist circumference (P=0.002] and weight (P = 0.01), while SNP-11391 was strongly associated with percent total body fat (P=0.000008]. Thus there might be linkage disequilibrium between SNP-11377 and SNP-1 1391. Our results suggest that SNP-11377 CG in the promoter region of adiponectin gene might be part of the genetic determinant for obesity, type 2 diabetes, dyslipidemia and hypertension, the components of metabolic syndrome. Finally, we recommend further extension of this study on larger sample size and study more SNPs in the adiponectin gene and with the presence of family pedigree a transmission disequilibrium test should be carried out to strengthen the statistical power of detection.
