Chromosome 2q12, the ADRA2B I/D polymorphism and metabolic syndrome.
OBJECTIVE
To test whether a previously hypertension-linked 23 cM region on chromosome 2 is linked to the metabolic syndrome (MetS) or its individual components, and whether a common I/D polymorphism of the adrenergic receptor 2b (ADRA2B) gene, mapping in that region, is associated with the same traits.


METHODS
We conducted fine mapping of the hypertension-linked region on chromosome 2 spanning between 107 and 130 cM using 11 informative polymorphic markers in 260 healthy white siblings belonging to 118 nuclear families. Variance-component linkage analysis was performed for each MetS component and a composite sum of MetS phenotypes 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 patients in the Malmö Diet and Cancer-cardiovascular arm, seeking for association with the MetS using standard definitions and separately, with its individual components.


RESULTS
For 24-h pulse pressure and waist/hip ratio, LOD [logarithm of the odds (to the base 10)] scores of more than two were found between 107 and 122 cM on chromosome 2. For the composite sum of MetS phenotypes, LOD score of more than 1 was found between 116 and 120 cM. There was no difference between carriers and noncarriers of the D-allele of the ADRA2B gene in MetS prevalence but D-carriers were associated with significantly higher levels of diastolic blood pressure.


CONCLUSIONS
Our results suggest that chromosome 2 could harbor one or more genes implied in blood pressure homeostasis and MetS development. The ADRA2B I/D polymorphism is not consistently associated with MetS and metabolic/anthropometric parameters but with diastolic blood pressure in an urban-based population of middle-aged Swedes.
Fava
Cristiano
C
Department of Clinical Sciences, University Hospital MAS, Malmö, Sweden. cristiano.fava@med.lu.se
Montagnana
Martina
M
Guerriero
Massimo
M
Almgren
Peter
P
von Wowern
Fredrik
F
Minuz
Pietro
P
Melander
Olle
O
D000328:Adult; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013548:Sweden
D018343:Receptors, Adrenergic, beta-2