4.2 Chromosome 2q12: the Adrenergic Receptor 2b (ADRA2b) Gene and Metabolic Syndrome in Swedish — is there a Link?

Introduction. Several linkage studies identified chromosome 2q12 as a hot spot for hypertension and other individual components of the metabolic syndrome (MetS). The common I/D polymorphism of the adrenergic receptor 2B (ADRA2B) gene, mapping in the same chromosomal region, was associated with hypertension and metabolic phenotypes.

Aim. To test if a 2 3 cM long region on chromosome 2 could be linked to metabolic syndrome (MetS) or its individual components and if a common I/D polymorphism of the ADRA2B gene mapping in that region is associated with the same traits.

Methods. 260 healthy, normotensive siblings belonging to 118 nuclear families from Malmö were included in the linkage analysis. We conducted a fine mapping of the region on chromosome 2 spanning between 107 to 130 cM using 11 informative polymorphic markers. Variance-component linkage analysis was performed for each MetS individual components and a composite sum of MetS phenotypes (MetS score) as quantitative trait after adjustment for significant covariates using ‘Solar software package’. Successively, the I/D polymorphism of the ADRA2B gene was genotyped in 5283 subjects recruited in the Malmö Diet and Cancer-cardiovascular arm (MDC-CVA) seeking for association with the MetS defined according to the NCEP/ATP III, the IDF and the European Group for the Study of Insulin Resistance (EGIR) criteria and, separately, with its individual components.

Results. For 24-hour pulse pressure and for the waist/hip ratio LOD score >2 has been found all over the region between 107 to 122 cM. For the MetS score, LOD score >1 has been found between 116 and 120 cM. Of the 5283 subjects included in the association analysis 21.8%, 29.3% and 20.5% resulted affected by MetS (according to the NCEP/ATP III, IDF and EGIR definition, respectively). There was no difference between carriers and non-carriers of the D-allele of the ADRA2B gene in MetS prevalence but D-carriers were associated with higher levels of diastolic BP (87.24+ /−9.43 vs 86.50+ /−9.35 mmHg; p=0.006).

Conclusions. Our results suggest that chromosome 2 could harbour one or more genes implied in BP homeostasis and MetS development. The ADRA2B I/D polymorphism is not associated with MetS and metabolic/anthropometric parameters whereas is associated with diastolic BP.