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Duration of diabetes and carotid wall thickness. The Insulin Resistance Atherosclerosis Study (IRAS).

BACKGROUND AND PURPOSE: Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. However, the role of the primary metabolic abnormality of diabetes (chronic hyperglycemia) in this disease process has not been fully elucidated. METHODS: A cross-sectional analysis was conducted among 489 persons with non-insulin-dependent diabetes mellitus; 299 were established diabetics (diagnosed previously) and 190 were newly diagnosed at the time of the Insulin Resistance Atherosclerosis Study (IRAS) examination. These men and women, of three different ethnic groups, were participants in IRAS. Established diabetes (versus newly diagnosed diabetes) and mean fasting glucose level were used as measures of hyperglycemic burden. Intimal-medial wall thickness (IMT) of the internal (ICA) and common (CCA) carotid arteries were used as indices of atherosclerosis. RESULTS: The mean duration of disease among established diabetics was 7 years. The mean CCA IMT and ICA IMT were 872 and 946 microns, respectively. Established diabetes and mean fasting glucose level were positively associated with increased CCA IMT (P < .05) but not ICA IMT, even after adjustment for numerous cardiovascular disease risk factors. CCA IMT was increased by 70 microns in established diabetics (versus newly diagnosed diabetics) and by 26 microns per 1 SD of fasting glucose. Among established diabetics, however, duration of known diabetes (number of years) was not significantly related to IMT. CONCLUSIONS: Among diabetics in IRAS, established diabetes and fasting glucose level were each independently associated with CCA IMT, suggesting that chronic hyperglycemia or its associated metabolic abnormalities may lead to increased risk of atherosclerosis.

Arteriosclerosis↗

Participation in voluntary individual savings accounts: an analysis of IRAs, 401(k)s, and the TSP.

New voluntary individual savings accounts have been proposed by some as a part of, or in addition to, Social Security. The success of these proposals would depend greatly on how many workers participate. This paper compares participation rates in three existing voluntary individual account-type plans--Individual Retirement Accounts (IRAs), 401(k)s, and the federal Thrift Savings Plan (TSP)--to clarify expectations about who might participate in a voluntary individual account system. It finds that participants in IRAs, 401(k)s, and the TSP tend to be disproportionately male, higher earners, older, full-time workers, and either white or nonblack minorities compared with the population at large. Differences in earnings explain much of the difference between participation rates of men and women, however, but less of the difference between participation rates of workers of different races. Whether participation in a new system of voluntary individual accounts would resemble participation in IRAs, 401(k)s, or the TSP would depend on a number of factors. For instance, the population covered by 401(k)s and the TSP is much smaller than that covered by Social Security. Average earnings are also higher among 401(k) and TSP participants than for workers covered by Social Security, which, based on these findings, suggests that participation rates could be lower in a universal system. Participation would also depend on many other factors, however, such as the extent of matching contributions or other financial incentives, the investment options available, and the amount of education provided to potential participants.

Black or African American↗

Metabolomic profiling of glucose homeostasis in African Americans: the Insulin Resistance Atherosclerosis Family Study (IRAS-FS).

INTRODUCTION: African Americans are at increased risk for type 2 diabetes. OBJECTIVES: This work aimed to examine metabolomic signature of glucose homeostasis in African Americans. METHODS: We used an untargeted liquid chromatography-mass spectrometry metabolomic approach to comprehensively profile 727 plasma metabolites among 571 African Americans from the Insulin Resistance Atherosclerosis Family Study (IRAS-FS) and investigate the associations between these metabolites and both the dynamic (SI, insulin sensitivity; AIR, acute insulin response; DI, disposition index; and SG, glucose effectiveness) and basal (HOMA-IR and HOMA-B) measures of glucose homeostasis using univariate and regularized regression models. We also compared the results with our previous findings in the IRAS-FS Mexican Americans. RESULTS: We confirmed increased plasma metabolite levels of branched-chain amino acids and their metabolic derivatives, 2-aminoadipate, 2-hydroxybutyrate, glutamate, arginine and its metabolic derivatives, carbohydrate metabolites, and medium- and long-chain fatty acids were associated with insulin resistance, while increased plasma metabolite levels in the glycine, serine and threonine metabolic pathway were associated with insulin sensitivity. We also observed a differential ancestral effect of glutamate on glucose homeostasis with significantly stronger effects observed in African Americans than those previously observed in Mexican Americans. CONCLUSION: We extended the observations that metabolites are useful biomarkers in the identification of prediabetes in individuals at risk of type 2 diabetes in African Americans. We revealed, for the first time, differential ancestral effect of certain metabolites (i.e., glutamate) on glucose homeostasis traits. Our study highlights the need for additional comprehensive metabolomic studies in well-characterized multiethnic cohorts.

Humans↗

Genetic epidemiology of insulin resistance and visceral adiposity. The IRAS Family Study design and methods.

PURPOSE: Insulin resistance and visceral adiposity are associated with increased risk of type 2 diabetes. In this report, we describe the methods of the IRAS Family Study, which was designed to identify the genetic and environmental risk factors for insulin resistance and visceral adiposity. METHODS: Families from two ethnic groups (African American and Hispanic) have been recruited from three clinical sites. Blood samples for DNA as well as other standard measures were collected. A CT scan (visceral adiposity) and a frequently sampled glucose tolerance test (insulin resistance) were performed. Preliminary estimates of heritability for indirect measures related to insulin resistance and visceral adiposity were obtained using a variance components approach in the first 93 families (approximately 1000 individuals). RESULTS: Estimates of heritability ranged from low (0.08) for fasting insulin and HOMA, to moderate (0.28) for fasting glucose, to high (0.54) for BMI. After adjustment for age, gender and ethnicity, all heritability estimates were significantly greater than zero (p < 0.05). CONCLUSIONS: These results are consistent with the expectation that intermediate measures of insulin resistance and visceral adiposity are heritable, and that the IRAS Family Study has statistical power to detect these intermediate phenotypes of type 2 diabetes and atherosclerosis.

Adipose Tissue↗

The infrared emission bands. III. Southern IRAS sources.

We present airborne 5-8 micrometers spectra of southern IRAS sources which reveal strong polycyclic aromatic hydrocarbon (PAH) emission features. The good correlation between the bands, in particular the dominant 6.2 and "7.7" micrometers features, strongly imply a common carrier, reinforcing the PAH hypothesis. However, small but detectable spectral variations exist. Planetaries have a distinctly different ratio of I(6.2)/I(7.7) than other nebulae, accompanied by a redward shift in the actual wavelength of the "7.7" micrometers peak. Further, we have detected a new feature, previously predicted from laboratory spectra of PAH molecules, at 5.2 micrometers in many of these sources. Spectra of two rare [WC 10] planetary nebular nuclei indicate a very prominent plateau of emission, linking the 6.2 and 7.7 micrometers bands. Several of our sources show definite evidence for emission structure between 14 and 23 micrometers in their IRAS Low-Resolution Spectral Atlas spectra: we attribute this structure to PAH bands. too. We have defined the "generic" spectrum of emission bands relating the mean intensities of each band to that of the strongest, near 7.7 micrometers. We have added three more planetary or protoplanetary nebulae to our correlation between 7.7 micrometers band intensity and nebular gas phase C/O ratio, namely NGC 6302, HR 4049, and the highly carbon-rich [WC 10] nucleus, CPD--56 degrees 8032. For the latter we have determined a ratio for C/O of approximately 4.8 from IUE observations. The good correlation between the intensity ratio of the "7.7" micrometers feature relative to the far-infrared dust continuum and nebular C/O also supports a carbonaceous carrier for these emission features.

Aircraft↗

Resolved CO (1 --> 0) Nuclei in IRAS 14348-1447: Evidence for Massive Bulge Progenitors to Ultraluminous Infrared Galaxies.

High-resolution, CO (1 --> 0) interferometry of the ultraluminous infrared galaxy IRAS 14348-1447 is presented. The merger system has a molecular gas mass of approximately 3x1010 M middle dot in circle and a projected nuclear separation of 4.8 kpc (3&farcs;5), making it one of the most molecular gas-rich galaxies known and an ideal candidate for studying the intermediate stages of an ultraluminous merger event. The CO morphology shows two molecular gas components associated with the stellar nuclei of the progenitors, consistent with the idea that the molecular disks are gravitationally bound by the dense bulges of the progenitor galaxies as the interaction proceeds. In contrast, less luminous infrared galaxies observed to date with projected nuclear separations of less, similar5 kpc show a dominant CO component between the stellar nuclei. This discrepancy may be an indication that the progenitors of mergers with lower infrared luminosity do not possess massive bulges and that the gas is stripped during the initial encounter. A comparison of the CO and radio luminosities of the northeast and southwest components of IRAS 14348-1447 show them to have comparable radio and CO flux ratios of f&parl0;NE&parr0;&solm0;f&parl0;SW&parr0; approximately 0.6, possibly indicating that the amount of star-forming molecular gas in the progenitors is correlated with the supernovae rate. The estimate of molecular gas masses of the nuclei and the extent of the radio emission are used to infer that the nuclei of IR 14348-1447 have gas densities comparable to the cores of elliptical galaxies.

Journal Article↗

Detection and Mapping of Decoupled Stellar and Ionized Gas Structures in the Ultraluminous Infrared Galaxy IRAS 12112+0305.

Integral field optical spectroscopy with the INTEGRAL fiber-fed system and Hubble Space Telescope optical imaging are used to map the complex stellar and warm ionized gas structure in the ultraluminous infrared galaxy IRAS 12112+0305. Images reconstructed from wavelength-delimited extractions of the integral field spectra reveal that the observed ionized gas distribution is decoupled from the stellar main body of the galaxy, with the dominant continuum and emission-line regions separated by projected distances of up to 7.5 kpc. The two optical nuclei are detected as apparently faint emission-line regions, and their optical properties are consistent with being dust-enshrouded weak [O i] LINERs. The brightest emission-line region is associated with a faint (mI=20.4), giant H ii region of 600 pc diameter, in which a young ( approximately 5 Myr) massive cluster of about 2x107 M middle dot in circle dominates the ionization. Internal reddening toward the line-emitting regions and the optical nuclei ranges from 1 to 8 mag in the visual. Taking the reddening into account, the overall star formation in IRAS 12112+0305 is dominated by starbursts associated with the two nuclei and corresponds to a star formation rate of 80 M middle dot in circle yr-1.

Journal Article↗

Ira Maximilian Altshuler: psychiatrist and pioneer music therapist.

The purpose of this study was to examine the life of Ira Maximilian Altshuler, psychiatrist and pioneer music therapist. In 1938, Dr. Altshuler initiated one of the first large-scale music therapy programs for mentally ill persons in the country at Detroit's Eloise Hospital. His innovative programs combined psychoanalytic techniques and music therapy methods specifically designed for use with large groups of clients. He later trained some of the first music therapy interns in the country, including Carol Collins, who served for many years as Professor of Music Therapy at Wayne State University, and Esther Goetz Gilliland, who later became President of NAMT. Dr. Altshuler promoted the practice and profession tirelessly, speaking to numerous audiences over the years and writing 19 articles about music therapy. Altshuler participated in the National Association for Music Therapy (NAMT) organizational meeting held in New York City in 1950. An active member of the organization for many years, he served on the Research Committee and hosted the 1955 national NAMT conference in Detroit. Even after Altshuler's retirement from Eloise Hospital in 1963, he remained active in numerous civic, music, and music therapy activities until his death 5 year later. Ira Altshuler should be remembered along with other music therapists from the time-Willem Van de Wall, Harriet Ayer Seymour and others-who vigorously embraced and advanced the status of the profession.

History, 20th Century↗

Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).

BACKGROUND: Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects. METHODS AND RESULTS: We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (S(I)) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), S(I), and fasting insulin and proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were consistent among the 3 ethnic groups of the IRAS. There was a linear increase in CRP levels with an increase in the number of metabolic disorders. Body mass index, systolic blood pressure, and S(I) were related to CRP levels in a multivariate linear regression model. CONCLUSIONS: We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to S(I). These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment strategies in healthy individuals with features of IRS.

Adult↗

Ira.

For a quarter of a century in genetics if you said Ira the chances were you meant Ira Herskowitz. When he died, on April 28 this year, it left a hole in the fields of genetics and genomics the size of the Grand Canyon.

Genomics↗

A tax strategy for healthcare workers. Section 403(b) plans are an alternative to weakened IRAs.

After the Tax Reform Act of 1986 reduced the tax-deduction benefits of investing in IRAs, many healthcare employees went looking for alternative tax-shelter investments. Several options are available. One alternative for taxpayers employed by tax-exempt organizations is Section 403(b) tax-deferred annuities (TDAs). Although the Tax Reform Act left Section 403(b) TDAs largely intact, it established a comprehensive set of nondiscrimination rules for certain statutory fringe-benefit plans--including Section 403(b) plans. The new rules are designed to restrict situations that favor participation by highly paid employees to the exclusion of other employees. Perhaps one of the harshest adjustments the 1986 law mandated is the imposition of an additional 10 percent income tax on withdrawals an investor makes from Section 403(b) plans before reaching the age of 59 years and 6 months. This excise tax had already applied to early withdrawals from an IRA, but the new law extends the penalty tax to cover all qualified plans, including TDAs.

Income Tax↗

Insulin secretion, obesity, and potential behavioral influences: results from the Insulin Resistance Atherosclerosis Study (IRAS).

BACKGROUND: This work was conducted to evaluate associations of insulin secretion with overall and central obesity, dietary fats, physical activity, and alcohol. METHODS: A frequently sampled intravenous glucose tolerance test (FSIGT) was used to assess acute insulin response to glucose (AIR) and insulin sensitivity (S(I)) among adult participants (n=675 with normal, NGT; n=332 with impaired glucose tolerance, IGT) in the Insulin Resistance Atherosclerosis Study (IRAS). Disposition index (DI) was calculated as the sum of the log-transformed AIR and S(I) to reflect pancreatic compensation for insulin resistance. Obesity was measured as body mass index (kg/m(2), BMI) and central fat distribution by waist circumference (cm). Dietary fat intake (total, saturated, polyunsaturated, oleic acid), physical activity, and alcohol intake were assessed by standardized interview. RESULTS: In unadjusted analyses, BMI and waist were each positively correlated with AIR among NGTs (r=0.26 and 0.23, respectively; p<0.0001) but correlations were weaker among the IGTs (r=0.10, NS; r=0.13, p<0.05 for BMI and waist, respectively). BMI and waist were inversely correlated with DI among NGTs (r=-0.13 and -0.20, respectively; p<0.0001) and among IGTs (r=-0.20 and -0.19, respectively, p<0.0001). Dietary fat variables were positively related, and alcohol was inversely related, to AIR among NGTs (p<0.01) but not among IGTs. With all factors considered simultaneously in a pooled analysis of IGTs and NGTs, waist, but not BMI, was positively associated with AIR (p<0.001) and inversely associated with DI (p<0.01). None of the behavioral variables were independently related to either outcome. CONCLUSION: Among non-diabetic patients, central obesity appears to be related to higher insulin secretion, but to lower capacity of the pancreas to respond to the ambient insulin resistance.

Adult↗

Abdominal obesity predicts declining insulin sensitivity in non-obese normoglycaemics: the Insulin Resistance Atherosclerosis Study (IRAS).

AIM: Cross-sectional studies have demonstrated a relationship between obesity and insulin sensitivity (S(I)); however, there is a lack of evidence from longitudinal studies. METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) estimated S(I) (x10(-4)/min.microU/ml) directly using a frequently sampled intravenous glucose tolerance test with minimal model analysis in 504 normoglycaemic subjects. Partial correlation coefficients (r) were calculated to compare the relationship of change in S(I) from baseline to 5 years later (DeltaS(I)) with baseline waist circumference (waist) as a measure of abdominal obesity and body mass index (BMI) as a measure of overall obesity. Mean DeltaS(I) was -1.06 (SD = 1.85). RESULTS: Higher baseline waist (r = -0.16; p = 0.0005), but not BMI (r = -0.005; p = 0.91), was associated with (-) DeltaS(I) in models including sex, ethnicity, clinical centre and baseline S(I), BMI, waist, age and physical activity. The waist-DeltaS(I) relationship differed across the levels of baseline BMI, being significant only in normal weight (r = -0.21) and overweight subjects (r = -0.16), but not in obese subjects. DeltaS(I) was correlated with a 5-year change in either obesity measure (Deltawaist: r = -0.22 and DeltaBMI: r = -0.20; p = 0.0001). CONCLUSIONS: Among non-diabetics, waist circumference was a strong predictor of declining S(I) among lean subjects, a modest predictor among overweight subjects, but was not predictive among obese individuals. Waist circumference should be considered, in addition to BMI, when identifying individuals at high risk of diabetes or the insulin resistance syndrome.

Abdomen↗

A genome scan for fasting insulin and fasting glucose identifies a quantitative trait locus on chromosome 17p: the insulin resistance atherosclerosis study (IRAS) family study.

Plasma insulin and glucose concentrations are important quantitative phenotypes related to diabetes and the metabolic syndrome. Reports purporting to identify quantitative trait loci (QTLs) that contribute to the variation in fasting insulin and glucose concentrations are discrepant. As part of the Insulin Resistance Atherosclerosis Study (IRAS) Family Study, a genome scan was performed in African-American (n = 42) and Hispanic (n = 90) extended families to identify regions that may contain positional candidate genes for fasting insulin and fasting glucose (n = 1,604 subjects). There was significant evidence for linkage of fasting insulin to the short arm of chromosome 17 (logarithm of odds [LOD] = 3.30; 54 cM between D17S1294 and D17S1299, P = 1.0 x 10(-4)). The strongest evidence for linkage over all pedigrees for fasting glucose was also observed in this region (LOD = 1.44; 58 cM, P = 9.9 x 10(-3)). The results of this study provide impetus for future positional cloning of QTLs regulating insulin and glucose levels. Identifying genes in these regions should provide insight into the nature of genetic factors regulating plasma glucose and insulin concentrations.

Black or African American↗

Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin Resistance and Atherosclerosis Study (IRAS).

OBJECTIVE: To evaluate the association of vitamin E with incidence of type 2 diabetes and to do so separately among individuals who did and those who did not report regular use of vitamin supplementation. RESEARCH DESIGN AND METHODS: The Insulin Resistance Atherosclerosis Study (IRAS) included 895 nondiabetic adults at baseline (including 303 with impaired glucose tolerance [IGT]), 148 of whom developed type 2 diabetes according to World Health Organization (WHO) criteria during the 5-year follow-up. At baseline, dietary vitamin E was estimated by a validated food frequency interview, usual supplement use was confirmed by supplement label, and plasma alpha-tocopherol was measured. Analyses were conducted separately for individuals who did (n = 318) and did not (n = 577) use vitamin E supplements. RESULTS: Among supplement nonusers, reported mean intake of vitamin E (mg alpha-tocopherol equivalents [alpha-TE]) did not differ between those who remained nondiabetic (n = 490) and those who developed diabetes (n = 87) (10.5 +/- 5.5 vs. 9.5 +/- 4.8 [means +/- SD], respectively, NS). After adjustment for demographic variables, obesity, physical activity, and other nutrients, the association remained nonsignificant (odds ratio [OR] 0.80, 95% CI 0.13-5.06) for the highest level of intake (> or =20 mg alpha-TE) compared with the lowest level (1-4 alpha-TE). However, results for plasma concentration of alpha-tocopherol showed a significant protective effect both before and after adjustment for potential confounders (adjusted OR 0.12, 95% CI 0.02-0.68, for the highest quintile vs. the lowest quintile; overall test for trend, P < 0.01). Among individuals who reported habitual use of vitamin E supplements (at least once per month in the year before baseline; 259 remained nondiabetic and 59 developed diabetes), no protective effect was observed for either reported intake of vitamin E or plasma concentration of alpha-tocopherol CONCLUSIONS: A protective effect of vitamin E may exist within the range of intake available from food. This effect may go undetected within studies of high-dose supplement use, which appears to hold no additional protective benefit.

Arteriosclerosis↗

The virulent bacteriophage IRA of Salmonella typhimurium: cloning of phage genes which are potentially lethal for the host cell.

Morphological and biological properties of Salmonella typhimurium phage IRA were studied. The phage is a member of the Styloviridae family and exhibits a very wide spectrum of lytic activity. Molecular cloning of phage genes whose expression is lethal for the host cell has been performed and consequences of gene expression have been investigated. Expression of recombinant plasmid pKI71 causes structural changes of the cell wall and also degradation of host DNA while plasmid DNA remains intact. Expression of pKI72 blocks normal cell division. The possibility of applying such recombinant clones in marking pathways of microbial contamination in water areas is proposed.

Bacteriolysis↗

Biophysics of T5, IRA phages, Escherichia coli outer membrane protein FhuA and T5-FhuA interaction.

In spite of the similarities in a structural organization of T5 and IRA phages their thermal and hydrodynamical peculiarities are completely different. One of the significant differences is observed in temperature value at which thermally induced DNA ejection starts. If in the case of physiological conditions this difference equals to 30 degrees capital ES, Cyrillic, then it decreases as ionic strength of the solvent decreases. Also, from our experimental results follows that in the opening of phage tail channel for T5 phage (at pH7) significant role-play electrostatic forces. In spite of that both of these phages grow on the same Escherichia coli strain, we have shown that these phages need different receptors to penetrate into the bacterial cell precisely FhuA serves as receptor only for T5 phage. The higher FhuA concentration in T5 phage suspension is, the more intensive DNA ejection in environment is. The minimal FhuA/T5 ratio, which is 300/1, correspondingly, necessary for effective DNA ejection from the phage head was experimentally determined. For the first time the ejection of T5 phage DNA induced by FhuA was observed in an incessant regime. The deconvolution of calorimetric curve of FhuA's denaturation has been shown that in a chosen condition there are four thermodynamically independent domains in the structure of FhuA.

Bacterial Outer Membrane Proteins↗

Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family Study.

Adiponectin, coded for by the APM1 gene, is a novel adipocyte-derived hormone implicated in energy homeostasis and obesity. Several genetic studies have observed evidence of association between APM1 gene polymorphisms and features of the metabolic syndrome, such as insulin resistance and obesity. As part of a comprehensive genetic analysis of the APM1 gene, we have screened 96 unrelated individuals for polymorphisms in the promoter, coding regions, and 3'untranslated region (UTR). Three promoter single-nucleotide polymorphisms (SNPs), two rare coding SNPs (G113A and T1233C), and 13 SNPs in the 3'UTR were identified. Eighteen SNPs were genotyped in 811 Hispanic individuals from 45 families in the IRAS Family Study (IRASFS). SNPs were tested for association with six obesity quantitative traits (body mass index, waist, waist:hip ratio, subcutaneous adipose tissue, visceral adipose tissue, and visceral:subcutaneous ratio). Significant evidence of association to at least one of the obesity traits was identified in seven of the 18 SNPs (<0.001-0.05). The promoter SNP INS CA-11156 was the most consistently associated SNP and was associated significantly with all measures of obesity, except the visceral:subcutaneous ratio (P-values 0.009-0.03). Haplotype analysis supported this evidence of association, with haplotypes containing an insertion of one CA repeat at position -11156 consistently being associated with lower obesity values (P-value <0.001-0.05). The adiponectin polymorphisms, in particular those in the promoter region, thus show significant association with obesity measures in the Hispanic population. Additional studies are needed to confirm our findings and determine which polymorphism causes the functional effect.

3' Untranslated Regions↗