Lack of association between a common polymorphism near the INSIG2 gene and BMI, myocardial infarction, and cardiovascular risk factors.
Epidemiological studies revealed an increasing prevalence of and a steep increase in obesity, a risk factor for cardiovascular disease. Because significant influence of a polymorphism, rs7566605, near the INSIG2 gene on BMI has been shown in the general population and in obesity cohorts, we hypothesized that this polymorphism might also act through an elevated BMI on the development of coronary artery disease (CAD) or myocardial infarction (MI). We pursued two strategies: First, the polymorphism rs7566605 was investigated for association with BMI, CAD/MI, and cardiovascular risk factors in a large German cohort at high risk for CAD and MI (n = 1,460 MI patients) as compared to unrelated healthy controls (n = 1,215); second, we extended our analyses on the families of MI patients and performed family-based association testing (n = 5,390 individuals). The polymorphism rs7566605 was analyzed using TaqMan technology. No deviation from Hardy-Weinberg equilibrium could be observed, and the call rate was 98.2%. No significant associations of rs7566605 with CAD/MI, BMI, and classical cardiovascular risk factors could be detected in the full sample size or in the subgroups. A total of 6,878 individuals were investigated in a population of German MI patients and their family members. Although the number of individuals was large enough, no influence of the rs7566605 INSIG2 polymorphism was detected on BMI and CAD/MI. We therefore conclude that in our sample the SNP rs7566605 near the INSIG2 gene does not influence BMI and is not associated directly with CAD/MI or indirectly through cardiovascular risk factors.
Wiedmann
Silke
S
Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
Neureuther
Katharina
K
Stark
Klaus
K
Reinhard
Wibke
W
Kallmünzer
Bernd
B
Baessler
Andrea
A
Fischer
Marcus
M
Linsel-Nitschke
Patrick
P
Erdmann
Jeanette
J
Schunkert
Heribert
H
Hengstenberg
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins