Frequency of rare mutations and common genetic variations in severe hypertriglyceridemia in the general population of Spain.
BACKGROUND
Hypertriglyceridemia (HTG) is a common complex metabolic trait that results of the accumulation of relatively common genetic variants in combination with other modifier genes and environmental factors resulting in increased plasma triglyceride (TG) levels. The majority of severe primary hypertriglyceridemias is diagnosed in adulthood and their molecular bases have not been fully defined yet. The prevalence of HTG is highly variable among populations, possibly caused by differences in environmental factors and genetic background. However, the prevalence of very high TG and the frequency of rare mutations causing HTG in a whole non-selected population have not been previously studied.


METHODS
The total of 23,310 subjects over 18 years from a primary care-district in a middle-class area of Zaragoza (Spain) with TG >500 mg/dL were selected to establish HTG prevalence. Those affected of primary HTG were considered for further genetic analysis. The promoters, coding regions and exon-intron boundaries of LPL, LMF1, APOC2, APOA5, APOE and GPIHBP1 genes were sequenced. The frequency of rare variants identified was studied in 90 controls.


RESULTS
One hundred ninety-four subjects (1.04%) had HTG and 90 subjects (46.4%) met the inclusion criteria for primary HTG. In this subgroup, nine patients (12.3%) were carriers of 7 rare variants in LPL, LMF1, APOA5, GPIHBP1 or APOE genes. Three of these mutations are described for the first time in this work. The presence of a rare pathogenic mutation did not confer a differential phenotype or a higher family history of HTG.


CONCLUSION
The prevalence of rare mutations in candidate genes in subjects with primary HTG is low. The low frequency of rare mutations, the absence of a more severe phenotype or the dominant transmission of the HTG would not suggest the use of genetic analysis in the clinical practice in this population.
['Lamiquiz-Moneo|Itziar|I|', 'Blanco-Torrecilla|Cristian|C|', 'Bea|Ana M|AM|', 'Mateo-Gallego|Rocío|R|', 'Pérez-Calahorra|Sofía|S|', 'Baila-Rueda|Lucía|L|', 'Cenarro|Ana|A|', 'Civeira|Fernando|F|', 'de Castro-Orós|Isabel|I|']
D000368:Aged D000072040:Apolipoprotein A-V D053304:Apolipoprotein C-II D001057:Apolipoproteins E D016022:Case-Control Studies D005260:Female D014644:Genetic Variation D006801:Humans D015228:Hypertriglyceridemia D008071:Lipoprotein Lipase D008297:Male D008565:Membrane Proteins D008875:Middle Aged D059645:Mutation Rate D018110:Receptors, Lipoprotein D013030:Spain
Mutations Hypertriglyceridemia Prevalence