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- Kathiresan, S., et al.
(author)
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Polymorphisms associated with cholesterol and risk of cardiovascular events
- 2008
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 358:12, s. 1240-1249
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Journal article (peer-reviewed)abstract
- Background: Common single-nucleotide polymorphisms (SNPs) that are associated with blood low-density lipoprotein (LDL) or high-density lipoprotein (HDL) cholesterol modestly affect lipid levels. We tested the hypothesis that a combination of such SNPs contributes to the risk of cardiovascular disease. Methods: We studied SNPs at nine loci in 5414 subjects from the cardiovascular cohort of the Malmo Diet and Cancer Study. We first validated the association between SNPs and either LDL or HDL cholesterol and subsequently created a genotype score on the basis of the number of unfavorable alleles. We used Cox proportional-hazards models to determine the time to the first cardiovascular event in relation to the genotype score. Results: All nine SNPs showed replication of an association with levels of either LDL or HDL cholesterol. With increasing genotype scores, the level of LDL cholesterol increased from 152 mg to 171 mg per deciliter (3.9 to 4.4 mmol per liter), whereas HDL cholesterol decreased from 60 mg to 51 mg per deciliter (1.6 to 1.3 mmol per liter). During follow-up (median, 10.6 years), 238 subjects had a first cardiovascular event. The genotype score was associated with incident cardiovascular disease in models adjusted for covariates including baseline lipid levels (P<0.001). The use of the genotype score did not improve the clinical risk prediction, as assessed by the C statistic. However, there was a significant improvement in risk classification with the use of models that included the genotype score, as compared with those that did not include the genotype score. Conclusions: A genotype score of nine validated SNPs that are associated with modulation in levels of LDL or HDL cholesterol was an independent risk factor for incident cardiovascular disease. The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors.
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- Kathiresan, Sekar, et al.
(author)
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Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
- 2008
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 189-97
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Journal article (peer-reviewed)abstract
- Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.
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- Simark-Mattsson, Charlotte, 1955, et al.
(author)
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Final pH affects the interference capacity of naturally occurring oral Lactobacillus strains against mutans streptococci.
- 2009
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In: Archives of oral biology. - : Elsevier BV. - 1879-1506 .- 0003-9969. ; 54:6, s. 602-7
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To establish the effects of three factors: previous caries experience; colonization of Streptococcus mutans; and final pH on autologous lactobacilli-mediated inhibition against a panel of mutans streptococci in young subjects with different caries experiences. DESIGN: The inhibition capacity was determined by the use of the agar overlay method and the final pH in culture medium was measured after 20 h. Using a logistic regression model, the risk of having an incomplete lactobacilli-mediated inhibition was calculated. RESULTS: All three factors significantly influenced the interference outcome in the order; final pH of the Lactobacillus strains, oral colonization of autologous S. mutans and caries experience. A high risk occurred at a lower pH and at a wider pH range for individuals with previous caries experience and autologous colonization of S. mutans compared with caries-free subjects who were not colonized. At a final pH of 4.0, this risk was approximately eight times higher than that of the latter group. Two mutans Streptococcus strains in the test panel demonstrated high individual predictive values of inhibition mediated by oral lactobacilli. CONCLUSIONS: Generation of a low pH either directly via organic acid production and/or production of bacteriocins or metabolites at a low pH may promote mutans Streptococcus growth inhibition, in vitro. Furthermore, a shift of pH range for the risk of incomplete inhibition of mutans streptococci suggests a less effective inhibition at a wider pH range for naturally occurring lactobacilli from individuals with earlier caries experience containing own S. mutans.
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- Simark-Mattsson, Charlotte, 1955, et al.
(author)
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Lactobacillus-mediated interference of mutans streptococci in caries-free vs. caries-active subjects.
- 2007
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In: European journal of oral sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 115:4, s. 308-14
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Journal article (peer-reviewed)abstract
- In order to assess whether naturally occurring oral lactobacilli have probiotic properties, lactobacilli were isolated from saliva and plaque from children and adolescents, with or without caries lesions. The interference capacities of these lactobacilli were investigated against a panel of 13 clinical isolates and reference strains of Streptococcus mutans and Streptococcus sobrinus, as well as against the subject's autologous mutans streptococci, using the agar-overlay technique. Lactobacillus-mediated inhibition differed significantly between the three subject groups (no caries, arrested caries, or active caries), demonstrating increased inhibition in subjects without present or previous caries experience compared to subjects with arrested caries or subjects presenting with frank lesions. Lactobacilli from subjects lacking S. mutans inhibited the growth of the test panel of mutans streptococci significantly better than lactobacilli from subjects who were colonized. Furthermore, subjects without caries experience harbored lactobacilli that more effectively repressed the growth of their autologous mutans streptococci. Twenty-three Lactobacillus spp. completely inhibited the growth of all mutans streptococci tested. Species with maximum interference capacity against mutans streptococci included Lactobacillus paracasei, Lactobacillus plantarum, and Lactobacillus rhamnosus. Naturally occurring oral lactobacilli significantly inhibited the growth of both test strains of mutans streptococci and the subject's autologous mutans streptococci in vitro, and this effect was more pronounced in caries-free subjects.
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