American journal of preventive medicine, Jan 16, 2015
Studies have demonstrated the benefit of weight loss and physical activity for diabetes preventio... more Studies have demonstrated the benefit of weight loss and physical activity for diabetes prevention among those with prediabetes. Despite this evidence, only about half of people with prediabetes report engaging in these behaviors. One presumed barrier is low patient awareness of prediabetes. The purpose of this study is to examine the impact of prediabetes awareness on the odds of engagement in diabetes risk-reduction behaviors. A pooled cross-sectional analysis of adults from two cycles (2007-2008, 2009-2010) of the National Health and Nutrition Examination Survey was conducted. Those with prediabetes were identified by excluding people with self-reported diabetes and then screening for hemoglobin A1c values between 5.7% and 6.4%. This group was then divided based on self-reported prediabetes. Multivariate logistic regression was used to estimate the effect of prediabetes awareness on the odds of engagement in physical activity, weight management, and the combination of physical ac...
Incentive programs directed at both providers and patients have become increasingly widespread. P... more Incentive programs directed at both providers and patients have become increasingly widespread. Pay-for-performance (P4P) where providers receive financial incentives to carry out specific care or improve clinical outcomes has been widely implemented. The existing literature indicates they probably spur initial gains which then level off or partially revert if incentives are withdrawn. The literature also indicates that process measures are easier to influence through P4P programs but that intermediate outcomes such as glucose, blood pressure, and cholesterol control are harder to influence, and the long-term impact of P4P programs on health is largely unknown. Programs directed at patients show greater promise as a means to influence patient behavior and intermediate outcomes such as weight loss; however, the evidence for long-term effects are lacking. In combination, both patient and provider incentives are potentially powerful tools but whether they are cost-effective has yet to be determined.
A significant proportion of the human genome is contained within haplotype blocks across which pa... more A significant proportion of the human genome is contained within haplotype blocks across which pairwise linkage disequilibrium (LD) is very high. However, LD is also often high between markers at more remote distances, and within different haplotype blocks. Here, we evaluate the origens of haplotype block structure in the three genes for alpha1 adrenergic receptors (alpha1-AR) in the human genome ( ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism (SNP) marker maps, and show that LD signals between distant markers are due to the presence of extended haplotype superblocks in individuals with ancient chromosomes which have escaped historic recombination. ARs mediate the physiological effects of epinephrine and norepinephrine, and are targets of many therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR missense variants, haplotype block structures in US Caucasians and African Americans, and haplotype tag SNPs for each block, and we present strong evidence for ancient haplotype block superstructure at these genes which has been partially disrupted by recombination, and evidence for reinstatement of linkage disequilibrium by subsequent recombination events. ADRA1A is comprised of four haplotype blocks in US Caucasians, while in African Americans Block 1 is split. ADRA1B has four blocks in US Caucasians, but in African Americans only the first two blocks are present. ADRA1D has two blocks in US Caucasians, and the first block is replaced by two smaller blocks in African Americans. For both ADRA1A and ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy in the human genome, which may reduce redundancy of testing by further aggregation of genotype data.
The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFal... more The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.
The beta-adrenergic receptors (b-AR) are G protein-coupled receptors activated by epinephrine and... more The beta-adrenergic receptors (b-AR) are G protein-coupled receptors activated by epinephrine and norepinephrine and are involved in a variety of their physiological functions. Previously, three b-AR genes (ADRB1, ADRB2 and ADRB3) were resequenced, identifying polymorphisms that were used in genetic association studies of cardiovascular and metabolic disorders. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: ADRB1 Arg389Gly and Gly49Ser, ADRB2 Arg16Gly and Gln27Glu, and ADRB3 Arg64Trp provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for each b-AR gene that included the known functional markers and also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 27 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations and for each gene, a single block with little evidence of historical recombination was observed. For each gene, haplotype captured most of the information content of each functional locus, even if that locus was not genotyped, and presumably haplotype would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using b-AR gene haplotype maps and marker panels as tools for linkage studies on b-AR function.
The alpha 2-adrenergic receptors (a 2 -AR) mediate physiological effects of epinephrine and norep... more The alpha 2-adrenergic receptors (a 2 -AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode a 2 -AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single nucleotide polymorphisms evenly spaced over the gene regions to identify gene haplotype block structure. A total of 24 markers were genotyped in 96 Caucasians and 96 African Americans. ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size, respectively, in both populations. ADRA2C had one haplotype block of 10 kb in Caucasians only. For the three genes, haplotype diversity and the number of common haplotypes were highest in African Americans, but a similar number of markers (3-6) per block was sufficient to capture maximum diversity in either population. For each of the three genes, the haplotype was capable of capturing the information content of the known functional locus even when that locus was not genotyped. The a 2 -AR haplotype maps and marker panels are useful tools for genetic linkage studies to detect effects of known and unknown a 2 -AR functional loci.
American journal of preventive medicine, Jan 16, 2015
Studies have demonstrated the benefit of weight loss and physical activity for diabetes preventio... more Studies have demonstrated the benefit of weight loss and physical activity for diabetes prevention among those with prediabetes. Despite this evidence, only about half of people with prediabetes report engaging in these behaviors. One presumed barrier is low patient awareness of prediabetes. The purpose of this study is to examine the impact of prediabetes awareness on the odds of engagement in diabetes risk-reduction behaviors. A pooled cross-sectional analysis of adults from two cycles (2007-2008, 2009-2010) of the National Health and Nutrition Examination Survey was conducted. Those with prediabetes were identified by excluding people with self-reported diabetes and then screening for hemoglobin A1c values between 5.7% and 6.4%. This group was then divided based on self-reported prediabetes. Multivariate logistic regression was used to estimate the effect of prediabetes awareness on the odds of engagement in physical activity, weight management, and the combination of physical ac...
Incentive programs directed at both providers and patients have become increasingly widespread. P... more Incentive programs directed at both providers and patients have become increasingly widespread. Pay-for-performance (P4P) where providers receive financial incentives to carry out specific care or improve clinical outcomes has been widely implemented. The existing literature indicates they probably spur initial gains which then level off or partially revert if incentives are withdrawn. The literature also indicates that process measures are easier to influence through P4P programs but that intermediate outcomes such as glucose, blood pressure, and cholesterol control are harder to influence, and the long-term impact of P4P programs on health is largely unknown. Programs directed at patients show greater promise as a means to influence patient behavior and intermediate outcomes such as weight loss; however, the evidence for long-term effects are lacking. In combination, both patient and provider incentives are potentially powerful tools but whether they are cost-effective has yet to be determined.
A significant proportion of the human genome is contained within haplotype blocks across which pa... more A significant proportion of the human genome is contained within haplotype blocks across which pairwise linkage disequilibrium (LD) is very high. However, LD is also often high between markers at more remote distances, and within different haplotype blocks. Here, we evaluate the origens of haplotype block structure in the three genes for alpha1 adrenergic receptors (alpha1-AR) in the human genome ( ADRA1A, ADRA1B and ADRA1D) by genotyping dense single-nucleotide polymorphism (SNP) marker maps, and show that LD signals between distant markers are due to the presence of extended haplotype superblocks in individuals with ancient chromosomes which have escaped historic recombination. ARs mediate the physiological effects of epinephrine and norepinephrine, and are targets of many therapeutic drugs. This work has identified haplotype backgrounds of alpha1-AR missense variants, haplotype block structures in US Caucasians and African Americans, and haplotype tag SNPs for each block, and we present strong evidence for ancient haplotype block superstructure at these genes which has been partially disrupted by recombination, and evidence for reinstatement of linkage disequilibrium by subsequent recombination events. ADRA1A is comprised of four haplotype blocks in US Caucasians, while in African Americans Block 1 is split. ADRA1B has four blocks in US Caucasians, but in African Americans only the first two blocks are present. ADRA1D has two blocks in US Caucasians, and the first block is replaced by two smaller blocks in African Americans. For both ADRA1A and ADRA1B, haplotype superstructures may represent a novel, higher-level hierarchy in the human genome, which may reduce redundancy of testing by further aggregation of genotype data.
The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFal... more The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.
The beta-adrenergic receptors (b-AR) are G protein-coupled receptors activated by epinephrine and... more The beta-adrenergic receptors (b-AR) are G protein-coupled receptors activated by epinephrine and norepinephrine and are involved in a variety of their physiological functions. Previously, three b-AR genes (ADRB1, ADRB2 and ADRB3) were resequenced, identifying polymorphisms that were used in genetic association studies of cardiovascular and metabolic disorders. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: ADRB1 Arg389Gly and Gly49Ser, ADRB2 Arg16Gly and Gln27Glu, and ADRB3 Arg64Trp provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for each b-AR gene that included the known functional markers and also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 27 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations and for each gene, a single block with little evidence of historical recombination was observed. For each gene, haplotype captured most of the information content of each functional locus, even if that locus was not genotyped, and presumably haplotype would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using b-AR gene haplotype maps and marker panels as tools for linkage studies on b-AR function.
The alpha 2-adrenergic receptors (a 2 -AR) mediate physiological effects of epinephrine and norep... more The alpha 2-adrenergic receptors (a 2 -AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode a 2 -AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single nucleotide polymorphisms evenly spaced over the gene regions to identify gene haplotype block structure. A total of 24 markers were genotyped in 96 Caucasians and 96 African Americans. ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size, respectively, in both populations. ADRA2C had one haplotype block of 10 kb in Caucasians only. For the three genes, haplotype diversity and the number of common haplotypes were highest in African Americans, but a similar number of markers (3-6) per block was sufficient to capture maximum diversity in either population. For each of the three genes, the haplotype was capable of capturing the information content of the known functional locus even when that locus was not genotyped. The a 2 -AR haplotype maps and marker panels are useful tools for genetic linkage studies to detect effects of known and unknown a 2 -AR functional loci.
Uploads
Papers by Ilona Lorincz