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Biomedical subjects

K Kontula

Publications and source records attributed to K Kontula.

At least 55 records · Page 3Linked to original sources
PubMed1999

Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects.

OBJECTIVES: This study was performed to evaluate the QT interval and heart rate responses to exercise and recovery in gene and mutation type-specific subgroups of long QT syndrome (LQTS) patients. BACKGROUND: Reduced heart rate and repolarization abnormalities are encountered among long QT syndrome (LQTS) patients. The most common types of LQTS are LQT1 and LQT2. METHODS: An exercise stress test was performed in 23 patients with a pore region mutation and in 22 patients with a C-terminal end mutation of the cardiac potassium channel gene causing LQT1 type of long QT syndrome (KVLQT1 gene), as well as in 20 patients with mutations of the cardiac potassium channel gene causing LQT2 type of long QT syndrome (HERG gene) and in 33 healthy relatives. The QT intervals were measured on electrocardiograms at rest and during and after exercise. QT intervals were compared at similar heart rates, and rate adaptation of QT was studied as QT/heart rate slopes. RESULTS: In contrast to the LQT2 patients, achieved maximum heart rate was decreased in both LQT1 patient groups, being only 76 +/- 5% of predicted in patients with pore region mutation of KvLQT1. The QT/heart rate slopes were significantly steeper in LQT2 patients than in controls during exercise. During recovery, the QT/heart rate slopes were steeper in all LQTS groups than in controls, signifying that QT intervals lengthened excessively when heart rate decreased. At heart rates of 110 or 100 beats/min during recovery, all LQT1 patients and 89% of LQT2 patients had QT intervals longer than any of the controls. CONCLUSIONS: LQT1 is associated with diminished chronotropic response and exaggerated prolongation of QT interval after exercise. LQT2 patients differ from LQT1 patients by having marked QT interval shortening and normal heart rate response to exercise. Observing QT duration during recovery enhances the clinical diagnosis of these LQTS types.

Adolescent↗
PubMed1999

Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts.

OBJECTIVES: The purpose of this study was to provide clinical and anatomical characteristics as well as genetic background of a malignant arrhythmogenic disorder. BACKGROUND: An inherited autosomally dominant cardiac syndrome causing stress-induced polymorphic ventricular tachycardia and syncope in the absence of structural myocardial changes was detected in two families. METHODS: Two unrelated families with six victims of sudden death and 51 living members were evaluated. Resting and exercise electrocardiograms (ECG), echocardiography, magnetic resonance imaging (MRI), cineangiography, microscopic examination of endomyocardial biopsies and a drug testing with a class IC antiarrhythmic agent flecainide were performed. A genetic linkage analysis was carried out to map the gene locus. RESULTS: Of the 24 affected individuals, 10 had succumbed with six cases of sudden death, and 14 survivors showed evidence of disease. Exercise stress test induced ventricular bigeminy or polymorphic ventricular tachycardia in affected individuals. Three children initially examined before 10 years of age developed arrhythmias during a four-year follow-up. Resting ECGs were normal in affected subjects except a slight prolongation of the QT intervals adjusted for heart rate (QTc) (430 +/- 18 vs. 409 +/- 19 ms, affected vs. nonaffected, p < 0.01). Administration of flecainide did not induce ECG abnormalities encountered in familial idiopathic ventricular fibrillation. Ventricular volumes, contractility and wall measurements were normal by echocardiography, right ventricular cineangiography and MRI. Histopathological examination showed no fibrosis or fatty infiltration. The cumulative cardiac mortality by the age of 30 years was 31%. The disease locus was assigned to chromosome 1q42-q43, with a maximal pairwise lod score of 4.74 in the two families combined. Only one heterozygous carrier was clinically unaffected suggesting high disease penetrance in adulthood. CONCLUSIONS: A distinct cardiac disorder linked to chromosome 1q42-q43 causes exercise-induced polymorphic ventricular tachycardia in structurally normal hearts and is highly malignant. Delayed clinical manifestation necessitates repeated exercise electrocardiography to assure diagnosis in young individuals of the families.

Adolescent↗
PubMed1999

Angiotensin converting enzyme gene insertion/deletion polymorphism, angiotensinogen gene polymorphisms, family history of hypertension, and childhood blood pressure.

Earlier epidemiologic studies have yielded inconsistent results on the extent and timing of the blood pressure (BP) increase in offspring of hypertensive parents. We hypothesized that a familial influence on the BP of the offspring exists from birth on, but becomes significant only later in childhood. We studied the influence of familial occurrence of hypertension on the BP of 3596 children aged 6 to 18 years during a 6-year follow-up. In addition, we examined the possible associations of BP variations with polymorphisms of two candidate genes for hypertension, ie, those coding for the angiotensin converting enzyme (ACE) and those coding for angiotensinogen. A positive family history of hypertension was reflected as the occurrence of higher systolic BP values from the age of 9 years and upward among the females and from the age of 12 years and upward among the males. The mean differences in BP varied from 3.2 to 5.8 mm Hg (systolic) and 2.1 to 5.9 mm Hg (diastolic) between the female offspring of normotensive and hypertensive parents and grandparents. The systolic BP values were significantly higher among females with a hypertensive history in two generations in comparison with females from normotensive families. Among the male offspring of hypertensive and normotensive families, the BP differences were inconsistent. The deletion/deletion males had higher systolic BP values than those with other ACE genotypes. In contrast, variation at the angiotensinogen gene locus was not significantly associated with BP. We conclude that parental history of hypertension is a risk factor for high blood pressure among the offspring from the ages of 9 to 12 years and upward, and hypertension within two generations may enhance this effect. Although the common genetic variation of ACE may influence blood pressure in male children and adolescents, our data do not suggest a role for the common variation of the angiotensinogen gene as a BP regulator during childhood.

Adolescent↗
PubMed1999

Arg506Gln factor V mutation and Val34Leu factor XIII polymorphism in Finnish patients with inflammatory bowel disease.

BACKGROUND: Earlier studies have indicated that inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with thromboembolic complications, whereas inherited disorders of coagulation occur less often than expected in IBD patients. The point mutation Arg506Gln of factor V (Factor V Leiden), resulting in resistance to activated protein C, is the commonest inherited form of thrombophilia. Alterations in circulating levels of factor XIII (FXIII) have been reported among IBD patients. We investigated whether Factor V Leiden or inherited Val34Leu polymorphism of FXIII would associate with IBD or its clinical outcome. METHODS: Factor V Leiden mutation and FXIII Val34Leu polymorphism were assayed in 328 unrelated Finnish patients with UC and 235 patients with CD by solid-phase minisequencing techniques. The control groups comprised 142 apparently healthy Finnish subjects and 120 Finnish blood donors. RESULTS: The frequency of Factor V Leiden mutation among IBD patients (4.5%) was not significantly different from that in subjects living in the same area (2.1%). No significant differences could be observed in the FXIII Val34Leu polymorphism allele frequencies between patients and controls. Clinical features of IBD, including the disease extent, requirement for immunosuppressive drugs, and occurrence of complications, seemed to be independent of these two clotting factor variants analyzed. CONCLUSIONS: Our data do not support an aetiologic or disease-modifying role for the factor V mutation or factor XIII Val34Leu polymorphism in IBD.

Adult↗
PubMed1999

Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension.

Components of the renin-angiotensin system play an important role in the normal regulation of blood pressure. We carried out a comprehensive genetic linkage study of the genes involved in the renin-angiotensin cascade in Finnish hypertensive twins and their affected siblings. We found no evidence for linkage between essential hypertension and the genes coding for renin, angiotensinogen, angiotensin-converting enzyme, or kallikrein 1 in the 329 hypertensive individuals of 142 families studied. In contrast, two intragenic markers for the type 1 angiotensin II receptor (AT1) showed some evidence for linkage in the total sample. A closer examination of this gene locus was carried out using subgroups of nonobese sibpairs with early onset of hypertension and uniform geographical origin. These stratifications yielded suggestive evidence for linkage of hypertension to the genetic area containing the AT1 gene, with a maximal multipoint logarithm of the odds (LOD) score of 2.9. A genetic association study carried out in an independent series of 50 hypertensive cases and 122 normotensive controls showed an increase in the frequency of the A1166-->C allele of the AT1 gene in the hypertensive individuals. In a novel variant of model-free multipoint linkage analysis allowing linkage disequilibrium in the calculations, an LOD score of 5.13 was obtained. Sequence analyses of the entire coding region and 848 bp of promoter region in the DNA sample on 8 index samples did not reveal previously unpublished sequence variations. The data provide evidence that a common genetic variant of the AT1 gene locus influences the risk of essential hypertension in the Finnish population.

Adult↗
PubMed1999

Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke.

BACKGROUND: It has recently been suggested that the Leu33Pro polymorphism of the platelet glycoprotein IIIa affects the risk of coronary thrombosis. Finland is genetically isolated and has an incidence of cardiovascular disease among the highest in the world. Interestingly, the prevalence of ischaemic heart disease also varies in different parts of the country, being highest in eastern Finland. METHOD: We studied the Leu33Pro polymorphism using polymerase chain reaction in 133 patients with coronary artery disease, 234 patients with cerebrovascular disease and 326 control subjects originating from two areas of Finland. RESULTS: The frequencies of the Pro33 allele in the patients with acute myocardial infarction and cerebrovascular attack were 13% and 14%, respectively, and did not differ from the controls (13%). Among patients with acute myocardial infarction from the Helsinki area, the family history of premature coronary artery disease was more often positive in carriers of the Pro33 allele than in non-carriers, but after adjustment for multiple comparisons the difference was no longer significant. CONCLUSIONS: We could not confirm the original observation that the Pro33 allele constitutes an independent risk factor for coronary artery disease. Further studies are needed to clarify whether co-occurrence of Pro33 and some unrecognized inherited factor pose an additional risk of vascular disease.

Adult↗
PubMed1999

Genetic association of alpha2-macroglobulin with Alzheimer's disease in a Finnish elderly population.

Recently, two studies have reported an association between the alpha2-macroglobulin gene on chromosome 12 and late-onset Alzheimer's disease, whereas others have not been able to replicate these findings. By using a prospective population-based study, we have investigated the relation between two polymorphisms in this gene with the presence of the disease and also with the extent of pathological changes in the cerebral cortex. The Vantaa 85+ Study includes all 601 persons, at least 85 years of age, who were living in Vantaa, Finland, on April 1, 1991. The neocortical beta-amyloid protein load and the number of neurofibrillary tangles were determined on tissue sections by using methenamine silver staining and a modified Bielschowsky staining, respectively. The A/A genotype in exon 24 of the alpha2-macroglobulin gene was associated with neuropathologically defined diagnosis of Alzheimer's disease according to the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria and with an increase in the neocortical beta-amyloid protein load. The effect of this association was stronger in the apolipoprotein E epsilon4-negative group. Therefore, genetic variability in the alpha2-macroglobulin gene is a risk factor associated with neuropathologically defined Alzheimer's disease in our population, as well as with the extent of neocortical beta-amyloid protein deposition.

Adult↗
PubMed1998

Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred.

At least three different gene loci were recently shown to account for the long QT syndrome (LQTS), a monogenic disorder with altered myocardial repolarization and occurrence of life-threatening cardiac arrhythmias. We screened 44 unrelated probands for mutations of the gene encoding the cardiac potassium channel KVLQT1 using single-strand conformational polymorphism (SSCP) and subsequent DNA sequencing. Two different mutations, T182I and D188N, were identified in two separate pedigrees. Cosegregation of the mutation with the disease phenotype was evident in both families. No mutations were identified at codon 212, previously suggested to represent a mutational hot spot of the KVLQT1 channel, in any of the 44 probands. The large pedigree with the D188N mutation (30 affected and 43 nonaffected individuals) permitted an analysis of expression of the mutant gene in its documented carriers. Although the mean (+/-SD) QTc interval was markedly longer in affected (484+/-38 ms) than in nonaffected individuals (406+/-27 ms, P < 0.001), there was a marked overlapping of individual values in these two groups. QTc values in symptomatic and asymptomatic carriers of the mutant gene were not significantly different. In conclusion, we have identified two novel mutations of the KVLQT1 component of a cardiac potassium channel. Our data support the functional significance of the pore-S6 domain of this membrane protein and emphasize the diagnostic usefulness of DNA analyses in families with LQTS.

DNA Mutational Analysis↗
PubMed1998

Functional analysis of the C(-188)A polymorphism of the human leptin promoter.

Mutational analysis of the promoter region of the leptin gene in morbidly obese Finnish subjects had revealed a previously unidentified C(-188)A polymorphism in the proximal promoter that showed a weak association with elevated serum leptin levels in obese male carriers of the variant (-188A) allele. In this study we demonstrated that neither expression of reporter gene constructs driven by wild-type (-188C) or variant (-188A) proximal promoter regions, nor assay of binding of cellular proteins reveal a genotype-related difference in promoter activity.

3T3 Cells↗
PubMed1998

Evaluation of QT interval duration and dispersion and proposed clinical criteria in diagnosis of long QT syndrome in patients with a genetically uniform type of LQT1.

OBJECTIVES: This study investigated the ability of QT duration, QT dispersion (QTD) and clinical diagnostic criteria to correctly identify genetically documented LQT1 type long QT syndrome (LQTS) patients, and to separate symptomatic and asymptomatic LQT1 patients. BACKGROUND: Ventricular repolarization has played an essential role both in diagnosis and risk assessment of LQTS. Today, molecular genetic techniques permit unequivocal identification of many LQTS patients. METHODS: QT interval and QTD in 12 symptomatic and 18 asymptomatic LQT1 patients and their 43 healthy relatives were evaluated. The sensitivity and specificity of upper normal limits of QT interval, two QT interval adjustment methods (Bazett's and Fridericia's formulas), and the proposed clinical criteria for LQTS were assessed. Occurrence of a mutant (D188N) KVLQT1 gene was considered as the basis of classification into affected and nonaffected individuals. RESULTS: Diagnostic sensitivity and specificity values were 90% and 88% using Bazett's formula, and 80% and 100% using Fridericia's cubic root formula or upper normal limits for QT interval. Suggested diagnostic criteria for LQTS reached 100% specificity, but 47% of the DNA-documented LQT1 patients were classified into the category of low or intermediate probability of LQTS. QT interval and heart rate did not differ between symptomatic (464 +/- 47 ms, 70 +/- 9 min(-1)) and asymptomatic 460 +/- 41 ms, 65 +/- 13 min(-1)) LQT1 patients. QTD was increased in symptomatic LQT1 patients compared to unaffected relatives (66 +/- 48 vs. 37 +/- 15 ms, p = 0.02), but symptomatic patients LQT1 did not differ from asymptomatic (45 +/- 19 ms). CONCLUSIONS: Not all LQT1 patients can be distinguished from healthy relatives by assessment of QT duration or clinical criteria. Presence of LQT1 gene can carry the risk of cardiac events even with no or only marginal prolongation of QT interval.

Adolescent↗
PubMed1998

A common pentanucleotide polymorphism of the 3'-untranslated part of the leptin receptor gene generates a putative stem-loop motif in the mRNA and is associated with serum insulin levels in obese individuals.

OBJECTIVE: To find out whether genetic alterations of the leptin receptor gene underlie human forms of obesity. DESIGN: Among 249 morbidly obese adults (body mass index, BMI > or = 40 kg/m2), we screened 30 patients with the highest serum leptin levels for alterations of their leptin receptor gene by single-strand conformation polymorphism (SSCP) technique. SUBJECTS: 249 severely obese subjects (present or past BMI > or = 40 kg/m2) and 138 lean controls (BMI < or = 25 kg/m2). MEASUREMENTS: DNA analysis was carried out using SSCP technique, sequencing and polymerase chain reaction (PCR) followed by digestion with the restriction enzyme Rsal. Serum leptin, glucose, insulin and lipid concentrations were determined in obese subjects. RESULTS: We were able to detect a pentanucleotide insertion (CTTTA) in the 3'-untranslated region of the leptin receptor gene. The presence of this pentanucleotide insert generates a putative stem-loop structure in the mRNA. Association studies were carried out on this variant. The frequency of the insertion allele did not differ between 249 obese (12.4%) and 138 lean (12.0%) subjects. There was no association of serum leptin, glucose or lipid levels with the pentanucleotide genotype in the obese individuals. However, when subjects without medication affecting insulin or glucose levels were considered, serum insulin levels were found to be lower in the heterozygous carriers of the insertion allele (15.1 +/- 9.2 mU/l) than in the subjects homozygous for the deletion allele (21.8 +/- 13.7 mU/l, P = 0.0035). CONCLUSIONS: We were able to confirm the presence of a frequent insertion/deletion polymorphism close to the 3'-end of the leptin receptor gene. We also showed that serum insulin levels in morbidly obese subjects are associated with 3'-UTR variant genotype.

Adult↗
PubMed1998

Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels.

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addition, we identified 1 carrier of the intron 14G-->A mutation of cholesterol ester transfer protein (CETP) in the high-HDL-C group and subsequently demonstrated cosegregation of the mutant allele with elevated HDL-C levels in the proband's family. In conclusion, we have identified a novel LCAT gene Gly230Arg mutation (LCAT[Fin]), which, together with the LPL Asn291Ser mutation, represents a relatively common genetic cause of diminishing HDL-C levels, at least among Finns. This article also reports occurrence of a CETP mutation in subjects having non-Japanese roots.

Adult↗
PubMed1998

Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme.

DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the XbaI polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.

Alleles↗
PubMed1997

Deletions of the low density lipoprotein receptor gene underlying familial hypercholesterolaemia: screening by polymerase chain reaction using pooled DNA and blood samples.

We evaluated the feasibility of methods based on the polymerase chain reaction (PCR) and non-automated or automated gel electrophoresis to detect clinically important DNA deletions in pooled DNA and blood samples. Two common low density lipoprotein (LDL) receptor mutations causing familial hypercholesterolaemia (FH) in the Finnish population were easily identified in pools corresponding to 20 individuals. One of these mutations (FH-North Karelia) deletes seven nucleotides from exon 6 of the LDL receptor gene. PCR amplification of DNA samples from the heterozygous patients with the FH-North Karelia gene results in the formation of DNA heteroduplexes, which markedly improves mutation detection. These studies show the applicability of semi-automated PCR techniques in the screening of DNA deletions and demonstrate the clinical diagnostic usefulness of heteroduplex formation.

Alleles↗
PubMed1997

Markers for the gene ob and serum leptin levels in human morbid obesity.

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 +/- 7 kg/m2, and 151 lean controls with a mean BMI of 22 +/- 2 kg/m2, and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI > or = 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders.

Adult↗
PubMed1997

Novel polymorphism of the human ob gene promoter in lean and morbidly obese subjects.

OBJECTIVE: Leptin, the circulating product of the human ob gene, may play role in control of appetite and metabolic rate. We screened the proximal promoter area of the ob gene for mutations and common polymorphisms in order to find out whether genetic variation in the regulatory area of this gene plays a role in human obesity. DESIGN: The technique of single-strand-conformation polymorphism (SSCP) was applied to screen for the promoter area of the ob gene for genetic alterations in morbidly obese patients. SUBJECTS: A total of 249 morbidity obese (present or past body mass index [BMI] > or = 40 kg/m2) and 141 lean (BMI < or = 25 kg/m2) subjects. MEASUREMENTS: DNA analysis was carried out using a single-strand conformation polymorphism (SSCP) technique and PCR followed by digestion with the restriction enzyme BssHll. Leptin was determined by radioimmunoassay in obese subjects. Serum lipids, glucose and insulin concentrations in the obese subjects were also determined. RESULTS: A new polymorphism C(-188)A was identified in the promoter region of the ob gene. This polymorphism was detected with allelic frequencies of 0.06 in morbidly obese subjects and 0.09 in lean controls (P = 0.28). Initial studies failed to show an association of this polymorphism with serum leptin, response to treatment for obesity, history and extent of weight gain, or serum insulin, glucose of lipid concentrations. CONCLUSIONS: We have identified a common polymorphism in the promoter area of the human ob gene which appears to be very useful for genetic association and linkage studies. Further studies are needed to elucidate its potential role in the regulation of the human ob gene and in human metabolic disorders.

Adolescent↗