Biomedical subjects

Y Antero Kesäniemi

Publications and source records attributed to Y Antero Kesäniemi.

At least 19 recordsLinked to original sources

PubMed2006

The effect of correcting for troponins on trends in coronary heart disease events in Finland during 1993-2002: the FINAMI study.

AIMS: The object of this study is to analyse the trends in coronary events in Finland during 1993-2002, correcting for the effect of troponins. METHODS AND RESULTS: A population-based myocardial infarction register recorded all coronary events (n=14 782) in four geographical areas of Finland during 1993-2002. Correction coefficients for the effect of troponins were calculated on the basis of 4359 coronary events, with simultaneous determination of troponins and the 'old' enzymatic markers of myocardial injury. Coronary mortality declined steeply, except in women aged > or = 75 years. The incidence of first coronary events declined 2.0% (95% confidence interval -3.0, -0.9%) per year among men and 1.0% (-2.7, 0.6%) per year among women aged 35-74 years. After correcting for the effect of troponins, also the decline among women became statistically significant: 2.7% (-4.5, -0.8%) per year. The effect of troponins tended to be stronger in women and older individuals than in men and younger individuals. The 28-day case fatality declined among men, but not among women. The effect of troponins on case fatality trends was weak. CONCLUSION: Declining trends in the incidence of coronary events in Finland during 1993-2002 were partly hidden by the effect of troponins. Both incidence and case fatality declines have contributed to the decline in mortality.

Adult↗

PubMed2006

A natural antibody to oxidized cardiolipin binds to oxidized low-density lipoprotein, apoptotic cells, and atherosclerotic lesions.

OBJECTIVE: Cardiolipin (CL) is found in membranes of bacteria, in the inner membrane of mitochondria and in plasma low-density lipoprotein (LDL). Anticardiolipin antibodies (aCL) are associated with disease states, and we have suggested that many aCL bind to oxidized CL (oxCL) but not native CL. To determine the immunogenicity and origins of oxCL in vivo, we cloned a natural antibody to oxCL. METHODS AND RESULTS: A monoclonal IgM antibody to oxCL (LRO1) was cloned from a nonimmunized LDLR-/- mouse. The V(H) sequence originated from the V(H)Gam3.8 germline with one nucleotide difference, and the Vkappa was 100% identical to Vkappa19-20 germline gene, making LRO1 a natural antibody. LRO1 bound specifically to oxCL and oxidized-LDL, but not to native CL or native LDL. LRO1 epitopes were demonstrated in apoptotic, but not in viable, Jurkat cells by flow cytometry, immunofluorescence and deconvolution microscopy. Human and rabbit atherosclerotic lesions contained LRO1 epitopes. Human LDL (n=113) showed LRO1 immunoreactivity, which correlated with aCL IgG titers (r=0.32, P=0.0004). CONCLUSIONS: These data demonstrate that some aCL antibodies are highly conserved natural antibodies binding to oxCL in oxLDL, apoptotic cells, and atherosclerotic lesions. This suggests that oxCL is one of the pathogen-associated molecular patterns of innate immunity and gives insight into the pathogenic events of diseases with increased titers of aCL antibodies.

Animals↗

PubMed2006

High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes.

OBJECTIVES: Resistin is a newly described hormone with a suggested role in insulin resistance. In humans, inflammatory cells seem to be the major source of resistin. The aim of this study was to find out whether plasma resistin concentration associates with carotid artery atherosclerosis and the risk factors of atherosclerosis. METHODS: Plasma resistin concentrations were measured in 525 Finnish middle-aged subjects among our population-based cohort. Intima-media thickness was measured from the internal carotid artery, the bifurcation enlargement, and the common carotid artery. RESULTS: Among all the subjects, the median resistin concentration was 7.07 ng/ml (interquartile range, 5.82-8.84), women having higher levels than men (P < 0.001) with median values of 7.56 ng/ml (6.18-9.19) and 6.67 ng/ml (5.63-8.31), respectively. Resistin level correlated negatively with mean intima-media thickness, internal carotid artery, and common carotid artery, but the association did not remain significant after adjustments. Plasma resistin concentration was associated positively with leukocytes (P < 0.001), highly sensitive C-reactive protein (P = 0.009), and IGF binding protein 1 (P < 0.001), but not with plasma insulin or glucose levels in analysis of covariance after adjustments for age, sex, and body mass index. CONCLUSIONS: The results imply that inflammatory factors are more important in the determination of plasma resistin concentration than plasma insulin or glucose values. Resistin is associated with proatherogenic inflammatory markers but not independently with early atherosclerosis.

Atherosclerosis↗

PubMed2006

Association between angiotensin-converting enzyme insertion/deletion polymorphism and treatment response in type 2 diabetic patients.

BACKGROUND: Our objective was to determine whether the angiotensin-converting enzyme insertion-deletion (ACE I/D) polymorphism affects the treatment responses in type 2 diabetic patients. METHODS: A total of 117 type 2 diabetic patients with poor metabolic control were evaluated and their treatment intensified before re-evaluation after a mean follow-up of 16.0 months. New insulin treatment was started in 61% of patients, the majority of whom used a combination of insulin and tablets. Earlier insulin treatment was continued and intensified for 9% of patients, and 19% of patients used oral treatment only. As antihypertensive treatment, 34% of patients used diuretics, 27% ACE-inhibitors, 38% beta-blockers and 21% calcium-channel blockers during the follow-up. For dyslipidemia, 6% of patients used fibrates and none used statins. RESULTS: There was a decrease in glycohemoglobin A1 levels [-2.0 (0.3) (S.E.) %], plasma total cholesterol [-0.2 (0.1) mmol/l] and plasma triglycerides [-1.2 (0.4) mmol/l], and an increase in plasma HDL cholesterol [0.07 (0.02) mmol/l] and weight [2.1 (0.5) kg] in response to intensified treatment. The changes in glycohemoglobin A1 (GHbA1) levels and HDL cholesterol were significantly associated with the ACE I/D polymorphism. The patients with the ACE I/I genotype had a greater decrease [-3.0 (0.7)] in their GHbA1 levels than the patients with I/D [-2.1 (0.5)] or D/D [-1.8 (0.4)] genotypes (P<0.03). HDL cholesterol levels increased more among the subjects homozygous for the I allele [0.21 (0.05)] than the I/D [0.04 (0.03)] or D/D [0.04 (0.03)] subjects (P<0.03). CONCLUSIONS: The results suggest that the ACE I/D polymorphism is associated with treatment responses in type 2 diabetic patients.

Journal Article↗

PubMed2006

Sequencing analysis of ghrelin gene 5' flanking region: relations between the sequence variants, fasting plasma total ghrelin concentrations, and body mass index.

Ghrelin is a 28-amino-acid peptide with several functions linked to energy metabolism. Low ghrelin plasma concentrations are associated with obesity, hypertension, and type 2 diabetes mellitus, whereas high concentrations reflect states of negative energy balance. Several studies addressing the hormonal and neural regulation of ghrelin gene expression have been carried out, but the role of genetic factors in the regulation of ghrelin plasma levels remains unclear. To elucidate the role of genetic factors in the regulation of ghrelin expression, we screened 1657 nucleotides of the ghrelin gene 5' flanking region (promoter and possible regulatory sites) for new sequential variations from patient samples with low (n = 50) and high (n = 50) fasting plasma total ghrelin concentrations (low- and high-ghrelin groups). Eleven single nucleotide polymorphisms (SNPs), 3 of which were rare variants (allelic frequency less than 1%) were found in our population. The genotype distribution patterns of the SNPs did not differ between the study groups, except for SNP-501A>C (P = .039). In addition, the SNP-01A>C was associated with body mass index (BMI) (P = .018). This variant was studied further in our large and well-defined Oulu Project Elucidating Risk for Atherosclerosis (OPERA) cohort (n = 1045) by the restriction fragment length polymorphism (RFLP) technique. No significant association of SNP-501A>C genotypes with fasting ghrelin plasma concentrations was found in the whole OPERA population. However, the association of this SNP with BMI and with waist circumference reached statistical significance in OPERA (P = .047 and .049, respectively), remaining of borderline significance for BMI after adjustments (P = .055). The results indicate that factors other than the 11 SNPs found in this study in the 5' flanking region of ghrelin gene are the main determinants of ghrelin plasma levels. However, SNP-501 A>C genotype distribution seems to be different in subjects having the highest compared with those with the lowest ghrelin levels, and the SNP may be associated with BMI and waist circumference.

5' Flanking Region↗

PubMed2006

Low plasma ghrelin concentration is an indicator of the metabolic syndrome.

BACKGROUND: Low ghrelin concentration has been associated with several features of metabolic syndrome (MS), but the relationship between ghrelin concentration and MS as a cluster of metabolic aberrations has not yet been studied. AIMS OF THE STUDY: To analyse whether ghrelin concentration is associated with MS. RESEARCH DESIGN AND METHODS: Fasting plasma ghrelin concentrations of the population-based cohort of 1037 middle-aged men and women were analysed using a commercial radioimmunoassay kit (Phoenix Peptide). MS was determined using the new International Diabetes Federation criteria. RESULTS: The prevalence of MS was 37.2%. The ghrelin concentrations were decreased in subjects with MS (635 pg/mL) compared to those without MS (687 pg/mL) (P=0.001). Ghrelin levels decreased with an increase in the number of metabolic abnormalities. Low ghrelin was a statistically significant predictor of MS in logistic regression analysis (P=0.005) so that the subjects in the 1st ghrelin quartile were at higher risk of having MS compared to the subjects in the 4th quartile (OR=1.82, 95% CI: 1.27-2.60, P=0.001). This association remained statistically significant after adjustment for age and sex (OR=1.76, 95% CI: 1.24-2.55, P=0.002). CONCLUSIONS: Metabolic syndrome is associated with low ghrelin levels suggesting a relationship of ghrelin in the metabolic disturbances of MS.

Biomarkers↗

PubMed2006

Functional significance of KCNH2 (HERG) K897T polymorphism for cardiac repolarization assessed by analysis of T-wave morphology.

BACKGROUND: Although KCNH2 (HERG) K897T polymorphism has been shown to be associated with the QT interval measured from 12-lead electrocardiogram (ECG), the functional significance of K897T polymorphism has been debated. The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. METHODS: Twelve-lead ECGs were digitized and T-wave morphology was analyzed with a PCA method in a population consisting of 228 healthy middle-aged subjects (121 women and 107 men). DNA samples were genotyped for the nucleotide 2690 A>C variation of the KCNH2 gene, corresponding to the KCNH2 K(lysine)897T(threonine) amino acid polymorphism. RESULTS: The allele frequencies were 0.86 (K) and 0.14 (T). The KCNH2 K897T polymorphism was associated with the total cosine R-to-T (TCRT), which reflects the wave front direction between depolarization and repolarization. TCRT was 0.421 in the genotype KK and 0.300 in the genotypes KT and TT (P = 0.04). The difference of TCRT was more marked between the KCNH2 K897T genotypes in women (P = 0.03) than in men (P = 0.52). CONCLUSIONS: The common K897T polymorphism of the cardiac potassium channel KCNH2 has functional significance for cardiac electrical properties. Subjects with a less common genotype, KT or TT, have smaller TCRT, which reflects dyssynchrony between depolarization and repolarization and is associated with an increased risk of cardiac mortality.

Adult↗

PubMed2006

Low plasma adiponectin concentration is an indicator of the metabolic syndrome.

OBJECTIVE: Adiponectin is an adipocytokine known to be decreased in obesity. It functions in glucose and fatty acid metabolism and also has an anti-inflammatory role in microvasculature. We wanted to investigate the role of adiponectin as a biomarker of metabolic syndrome (MS) and see how the plasma adiponectin levels relate to new criteria of MS proposed by the International Diabetes Federation. METHODS: Plasma adiponectin concentrations were measured from total of 1041 Finnish subjects with an ELISA - a novel method planned in our laboratory. RESULTS: In both the sexes, the plasma adiponectin levels were lower in subjects with MS when compared with subjects with no diagnosis of MS (P< 0.001). Plasma adiponectin levels did not differ between subjects with National Cholesterol Education Program (ATPIII) and International Diabetes Federation-defined MS. Lower adiponectin levels were associated with different components of the MS and there was a trend towards decreasing adiponectin levels with an increasing number of components of MS in both the sexes. Subjects in the lowest adiponectin quartile had a significantly higher probability of having MS (P< 0.001), 4.4-fold in males and 7.5-fold in females, when compared with the corresponding individuals in the highest quartile. The probability increased in every lowering quartile of adiponectin level and was independent of body mass index. CONCLUSION: We conclude that adiponectin levels correlate with most of the components of the MS and the metabolic cluster per se.

Adiponectin↗

PubMed2005

Coronary heart disease: from a disease of middle-aged men in the late 1970s to a disease of elderly women in the 2000s.

AIMS: To analyse secular changes in the prevalence of coronary heart disease (CHD) and to assess changes in the burden of CHD at population level. METHODS AND RESULTS: Data were used from two large cross-sectional health examination surveys representing the entire Finnish adult population in 1980 and 2000. In the 1978-80 survey, the sample covered 5101 individuals aged > or =45, of whom 88% participated. The 2000-2001 survey comprised 5310 individuals in the same age range. Participation rate in the health examination was 87%. Prevalence of CHD decreased in men and women under the age of 65 and increased among those aged > or =75. Prevalence of large Q-waves indicating previous myocardial infarction decreased in all male age groups and in women aged 65-74. The total estimated number of persons with CHD increased by 18% (95% CI=6-30) during the past 20 years in Finland. In 1980, the most dominant CHD group was men aged 45-64, whereas in 2000, women aged > or =75 comprised the largest CHD group. CONCLUSION: Although the prevalence of CHD has decreased among middle-aged persons, the number of CHD cases has increased during the past 20 years in Finland.

Age Distribution↗

PubMed2005

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

Adult↗

PubMed2005

A new definition for myocardial infarction: what difference does it make?

AIMS: As a response to changing diagnostic tools of myocardial infarction (MI), new case definitions for acute coronary events were published in 2003 as the American Heart Association Scientific Statement. We assessed the new definition in hospitalized patients in a large population-based MI register study. METHODS AND RESULTS: We identified all suspected acute coronary syndromes with data either on troponin T or on troponin I and at least one of the enzymatic markers of myocardial injury (n=6104). The 2003 definition with the use of troponins identified 83% more definite MIs than the WHO MONICA definition using cardiac enzymes. The additional patients were older, had more often diabetes, and received less often thrombolysis and revascularization than those having MI by both definitions. Adjusting for age, sex, study area, and study year, the additional patients with their first MI aged 25-74 had a higher risk of cardiovascular death within 1 year than patients having definite MI by both definitions (hazard ratio 1.6, 95% CI 1.1-2.2). CONCLUSION: The changing diagnostic criteria present a considerable challenge for the assessment of long-term trends in MI events in the community as well as for longitudinal studies of the natural history of MI. The 2003 definition, when applied using troponins, identified a sizable new group of MI patients, among persons with suspected acute coronary syndrome, at high risk of a recurrent event.

Adult↗

PubMed2005

Estrogen replacement therapy increases plasma ghrelin levels.

Ghrelin is a novel peptide hormone that has GH releasing activity and also other endocrine and metabolic functions. The purpose of this study was to investigate the effects of estrogen replacement therapy on plasma active ghrelin levels in 64 hysterectomized postmenopausal women receiving peroral estrogen (PE) or transdermal estrogen therapy for 6 months. Active ghrelin was measured using commercial RIA. Estrogen therapy increased plasma active ghrelin from 479 +/- 118 to 521 +/- 123 pg/ml (P = 0.002) among all the study subjects. PE therapy increased plasma ghrelin levels from 465 +/- 99 to 536 +/- 104 pg/ml (P = 0.001). Transdermal estrogen therapy did not increase plasma ghrelin levels significantly (from 491 +/- 132 to 509 +/- 138 pg/ml; P = 0.332). The relative changes in plasma ghrelin levels were associated with the relative changes in serum estradiol concentrations (r = 0.299; P = 0.017). During the estrogen therapy, negative associations were found between plasma active ghrelin levels and several plasma lipids (total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total triglycerides, and very low-density lipoprotein triglycerides). As a conclusion, estrogen replacement therapy increased active plasma ghrelin levels, particularly PE therapy. Additional studies are needed to determine the possible underlying mechanisms.

Aged↗

PubMed2005

Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project).

Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides (<25th and >75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). One thousand four hundred thirty-six (854 men/582 women) affected patients by our criteria were compared with 1,672 (737 men/935 women) unaffected persons. Affected patients had more hypertension, obesity, and hyperglycemia, and they met a higher number of ATP-III criteria (3.2 +/- 1.1 SD vs 1.3 +/- 1.1 SD, p <0.001). Overall, 76% of affected persons also qualified for the ATP-III definition (Cohen's kappa 0.61, 95% confidence interval 0.59 to 0.64), similar to a separate group of 464 sporadic, unrelated cases (75%). Concordance increased from 41% to 82% and 88% for ages < or =35, 36 to 55, and > or =55 years, respectively. Affected status was also independently associated with waist circumference (p <0.001) and fasting glucose (p <0.001) but not systolic blood pressure (p = 0.43). Thus, the lipid-based criteria used to define affection status in this study substantially parallels the ATP-III definition of metabolic syndrome in subjects aged >35 years. In subjects aged <35 years, atherogenic dyslipidemia frequently occurs in the absence of other metabolic syndrome risk factors.

Adolescent↗

PubMed2005

Role of candidate genes in the lipid responses to intensified treatment in Type 2 diabetes.

OBJECTIVE: To identify genetic factors related to individual differences in lipid responses to intensified treatment in Type 2 diabetes. DESIGN AND METHODS: After evaluation and intensification of their treatment, 107 Type 2 diabetes patients with poor metabolic control were re-evaluated after mean follow-up time of 15.6 (0, 4) (SE) months. The genes coding major lipid regulatory proteins and their relations to plasma lipid and lipoprotein changes were studied. RESULTS: During the follow-up, levels of glycohemoglobin A1 (GHBA1) decreased (-1.7%), plasma HDL cholesterol (+0.05 mmol/l) and lipoprotein (a) [Lp(a)] (+4.2 mg/dl) increased, while triglyceride (TG) levels decreased (-1.2mmol/l) despite mean weight gain of 2.1 kg (p from <0.01 to <0.001). Of the gene markers studied, the lipoprotein lipase (LPL) Pvull (p=0.005) independently affected changes in HDL-cholesterol and was associated with the frequency of coronary heart disease (CHD). Lp(a) changes were associated with apolipoprotein B (ApoB) Glu4154Lys polymorphism (p=0.004). CONCLUSIONS: These results suggest that genetic variations at LPL and ApoB loci are among the factors contributing to the variability in response to lipid parameters to therapy in Type 2 diabetes. LPL Pvull rare allele homozygote status seems to be beneficial with more favorable lipid changes and protection against CHD.

Alleles↗

PubMed2005

Prevalence, characteristics and natural course of inappropriate sinus tachycardia.

AIMS: To study the prevalence, characteristics and natural course of inappropriate sinus tachycardia (IST). METHODS AND RESULTS: The prevalence and characteristics of IST were evaluated in a random sample of 604 middle-aged subjects. Seven of the subjects (1.16%) fulfilled the contemporary diagnostic criteria of IST. The systolic (147+/-11 mmHg vs. 130+/-13 mmHg, P<0.001) and diastolic ambulatory blood pressures (92+/-7 mmHg vs. 81+/-8 mmHg, P<0.001) were higher among the subjects with IST than among the controls. The other laboratory, echocardiographic and personality measurements, with the exception of the hostility score (10+/-2 vs. 8+/-3, P<0.001), revealed no differences between the groups. The natural course and prognosis of the disorder was assessed among the subjects fulfilling the IST criteria and nine previously diagnosed IST patients. During a mean follow-up of 6.0+/-2.4 years, none of the subjects developed any clinical or echocardiographic evidence of structural heart disease despite ongoing palpitations, and there was no significant reduction in the 24-h average HR (9+/-2 bpm vs. 89+/-8 bpm, P=0.204). CONCLUSION: The prevalence of IST in a middle-aged population was higher than previously assumed. Despite the chronic nature of the disorder, the prognosis of IST was benign. The causal relationship between IST and hypertension and/or hostile personality type remains speculative.

Chi-Square Distribution↗

PubMed2005

The -1C to T polymorphism in the annexin A5 gene is not associated with the risk of acute myocardial infarction or sudden cardiac death in middle-aged Finnish males.

OBJECTIVE: A common polymorphism (-1C to T) in the translation initiation sequence of annexin A5 (ANV) gene has recently been associated with a decreased risk of acute myocardial infarction (AMI). The aim of the present study was to analyze the association between the ANV genepolymorphism and the risk of AMI and ischemic sudden cardiac death (SCD) in middle-aged Finnish males. MATERIAL AND METHODS: A case-control study involving three distinct groups of subjects was carried out: (1) victims of SCD (n=98), (2) survivors of AMI (n=212), and (3) randomly selected control subjects without any history of coronary heart disease (n=243). The ANV polymorphism was genotyped in each study group. RESULTS: Among the control group of healthy Finnish males the prevalence rates of the CC, CT, and TT genotypes were 83.1%, 15.2%, and 1.6%, respectively. Among the survivors of AMI, the prevalence rates of CC, CT, and TT were 79.7%, 20.3%, and 0%, respectively, and among the victims of SCD 83.7%, 16.3%, and 0%, respectively. No significant differences in the genotype or allele distributions were observed between the study groups. CONCLUSION: The -1C to T polymorphism in the ANV gene is not associated with the risk of AMI or SCD in middle-aged Finnish males.

5' Untranslated Regions↗

PubMed2005

Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study.

AIMS/HYPOTHESIS: Adiponectin is an adipocytokine with lowered blood levels in obesity and Type 2 diabetes mellitus. We sought to define the specific effects of different alleles of the gene encoding adiponectin. METHODS: We studied the associations of adiponectin gene sequence variations with body fat distribution and insulin indices in 503 White and 276 Black subjects of the HERITAGE Family Study cohort and subjects from a Finnish population. RESULTS: The His111 allele frequency of the Tyr111 His polymorphism in Finnish Type 2 diabetic subjects (n=254) was higher (5.1%) than in control subjects (n=270) (2.6%; P = 0.033). In the HERITAGE cohort, the His111 allele was associated with a lower insulin sensitivity index (P = 0.018) and a higher acute insulin response to glucose (P = 0.0098) in Whites. Other variants showed associations with adiposity and plasma lipid values only in Blacks. Among Blacks, the IVS2+G62T variant was associated with body fat (P = 0.002) and total cholesterol values (P = 0.005), and the Gly15Gly variant with cholesterol (P = 0.009) and triglyceride (P = 0.05) levels. The haplotype derived from these two polymorphisms was associated with total body fat, while the IVS2+G62T and Tyr111His-haplotype was associated with body fat and disposition index. CONCLUSIONS: The carriers of the His111 allele may have a higher risk of developing Type 2 diabetes mellitus. Racial differences were found between Blacks and Whites in body composition and lipids according to ACDC genotypes. Sequence variants in the adiponectin gene appear to be associated with diabetes and diabetes-related phenotypes.

Adipocytes↗

PubMed2005

IGF-I concentrations are positively associated with carotid artery atherosclerosis in women.

BACKGROUND: Alterations in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF-I levels. AIMS: To investigate whether IGF-I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery. METHODS: Fasting plasma IGF-I concentrations (n=1008) were measured in a large population-based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method. RESULTS: Low IGF-I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C-reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF-I concentrations were positively associated with the mean IMT of women (ss=0.127, P=0.009) whereas the association in men was weaker and negative (ss=-0.088, P=0.034). The 1169A allele was associated with low low-density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women. CONCLUSIONS: IGF-I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF-I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.

Atherosclerosis↗