The Renalase Asp37Glu polymorphism is not associated with hypertension and cardiovascular events in an urban-based prospective cohort: the Malmö Diet and cancer study.
BACKGROUND
Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies delineate a possible role of this enzyme in blood pressure (BP) maintenance and cardiac protection and two single nucleotide polymorphisms, RNLS rs2576178 A > G and rs2296545 C > G have been associated with hypertension. The latter SNP leads to a non synonymous Asp to Glu substitution deleting a flavin adenine dinucleotide (FAD) binding site with possible impaired functionality. We tested the hypothesis that these polymorphisms could affect BP levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes.


METHODS
The polymorphisms were genotyped in 5696 participants of the population-based Cardiovascular Cohort of the "Malmö Diet and Cancer" (MDC-CC). The incidence of cardiovascular events (coronary events [n = 408], strokes [n = 330], heart failure [n = 190] and atrial fibrillation/flutter [n = 406]) was monitored for an average of approximately 15 years of follow-up.


RESULTS
Both before and after adjustment for sex, age and BMI the polymorphisms did not show any effect on BP level and hypertension prevalence. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for cardiac and cerebrovascular events was not significantly different in carriers of different genotypes. A significant interaction was found between the rs2296545 C > G and age with respect to BP/hypertension.


CONCLUSIONS
Our data do not support a major role for these RNLS polymorphisms in determining BP level and incident events at population level. The positive interaction with age suggest that the effect of the rs2296545 C > G polymorphism, if any, could vary between different ages.
Department of Clinical Sciences, Lund University, University Hospital of Malmö, Sweden. cristiano.fava@med.lu.se
Cristiano
C
Fava
Martina
M
Montagnana
Elisa
E
Danese
Marketa
M
Sjögren
Peter
P
Almgren
Gunnar
G
Engström
Bo
B
Hedblad
Gian Cesare
GC
Guidi
Pietro
P
Minuz
Olle
O
Melander
D000367:Age Factors; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006306:Health Surveys; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology / Q000235:genetics
D008995:Monoamine Oxidase; C521557:renalase