Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: family-based study

Abstract

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value=0.001), waist circumference (p-value=0.037), BMI (p-value=0.015) and percentage of total body fat (p-value=0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.

Keywords: ADIPOQ; BMI; DBP; DNA; HDL; HOMA-IR; IDF; International Diabetes Federation; LDL; LOD; MGA; Measured genotype analysis; Obesity; PCR; PPARγ; Pedigree; QTL; SBP; SNP; SOLAR; Sequential Oligogenic Linkage Analysis Routines; T2DM; TG; VLDL; adiponectin; body mass index; dNTPs; deoxyribonucleic acid; diastolic blood pressure; dideoxynucleotides; high density lipoprotein; homeostasis model of assessment-insulin resistance; logarithm (base 10) of odds; low density lipoprotein; measured genotype analysis; peroxisome proliferator activated receptor gamma; polymerase chain reaction; quantitative trait locus; single nucleotide polymorphism; systolic blood pressure; triglycerides; type 2 diabetes mellitus; very low density lipoprotein.