Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects.

An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.     

Thr54 allele of the FABP2 gene affects resting metabolic rate and visceral obesity

We investigated the relationship between Ala54Thr variant allele of the fatty acid-binding protein 2 (FABP2) gene (Ala54Thr) and development of obesity in Japanese obese women. FABP2 genotypes were determined with a fluorescent allele-specific DNA primer assay system. Body weight, waist and hip circumference, amounts of visceral and subcutaneous white adipose tissue measured by computed tomography (CT) were compared between subjects with Thr allele and without Thr allele before and after the diet and exercise therapy in 80 Japanese obese women. The frequency of the Thr54 allele did not differ between obese and control subjects (0.388 versus 0.329, respectively). In subjects with Ala/Thr and Thr/Thr genotype, adjusted resting metabolic rate (RMR) was significantly lower than the subjects with Ala/Ala genotype. Subjects with the Thr54 allele showed significantly greater waist circumference after diet and exercise therapy than subjects with Ala/Ala genotype. They also demonstrated greater body weight at 20 years of age compared to subjects with Ala/Ala genotype. In conclusion, Thr54 allele of FABP2 has associations with lower adjusted resting metabolic rate, resistance in reducing visceral white adipose tissue (WAT) and early onset of obesity in Japanese obese women.     

Thr54 allele carriers of the Ala54Thr variant of FABP2 gene have associations with metabolic syndrome and hypertriglyceridemia in urban South Indians

The intestinal fatty acid-binding protein gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty acid absorption and metabolism. This study investigates the association of the Ala54Thr variant of the intestinal fatty acid-binding protein gene on type 2 diabetes mellitus and other related metabolic traits in Asian Indians. Ala54Thr polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism in unrelated 773 type 2 diabetic and 899 normal glucose-tolerant (NGT) subjects, randomly chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in South India. The Ala54Thr polymorphism was not associated with type 2 diabetes mellitus or obesity. However, genotype-phenotype study revealed that the NGT subjects carrying the Thr54 allele had significantly higher 2-hour plasma glucose (P = .007), glycated hemoglobin (P = .004), 2-hour insulin (P = .027), and fasting low-density lipoprotein cholesterol (P = .032) levels compared with those with the Ala54 allele. Normal glucose-tolerant subjects with Ala54Thr and Thr54Thr genotypes had significantly higher fasting serum triglyceride levels (P = .003) compared with those with Ala54Ala. The subjects were stratified into those with hypertriglyceridemia (serum triglyceride levels >or=150 mg/dL) and those without. The odds ratio for hypertriglyceridemia for the individuals carrying the Ala54Thr genotype was 1.491 (95% confidence interval [CI], 1.22-1.83, P < .0001), and for those carrying the Thr54Thr genotype, it was 1.888 (95% CI, 1.34-2.67; P < .0001). Subjects were also stratified into those with metabolic syndrome (MS) and those without, according to modified Adult Treatment Panel III guidelines. The odds ratio (adjusted for age and sex) for MS for the individuals carrying the Ala54Thr genotype was 1.240 (95% CI, 1.02-1.51; P = .03), whereas for those carrying the Thr54Thr genotype, it was 1.812 (95% CI, 1.28-2.57; P = .001). Carriers of the Thr54 allele have associations with MS and hypertriglyceridemia in this urban South Indian population.     

Lack of association between the fatty acid binding protein 2 (FABP2) polymorphism with obesity and insulin resistance in two aboriginal populations from Chile

Abstract The aim of this study was to assess the frequency of fatty acid binding protein 2 (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with obesity and insulin resistance in Chilean aboriginal populations. A sample of 96 urban Aymara and 111 urban Mapuche subjects aged 20–80 years were recruited for this cross-sectional study. Glucose, insulin and lipid profile were measured in fasting plasma samples. Insulin resistance was estimated through the HOMA-IR model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis. The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects, which is one of the lowest reported to date. The corresponding frequency in Mapuche subjects was 31.9% (p<0.002). Regarding genotype–phenotype associations, no significant differences were found in any of the anthropometric or metabolic variables according to Ala54Thr genotypes. After adjustment by BMI and metabolic variables through a logistic regression analysis, the association of the FABP2 polymorphism with ethnic group persisted (Mapuche group: OR=2.37, 95% CI 1.319–4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays a relevant role in obesity and insulin resistance in Chilean ethnic groups.     

Association between neuromedin U gene variants and overweight and obesity

BACKGROUND: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean. OBJECTIVE: Our objective was to investigate whether variants in NMU are associated with human obesity. DESIGN: The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population. SETTING: The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic. SUBJECTS AND METHODS: A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects. RESULTS: The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2-0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2) [odds ratio, 2.5 (1.2-5.3); P = 0.01]. CONCLUSION: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.     

Thr-encoding allele homozygosity at codon 54 of FABP 2 gene may be associated with impaired delta 6 desatruase activity and reduced plasma arachidonic acid in obese children

BACKGROUND: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. AIM: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. METHODS: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. RESULTS: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p < 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p < 0.05, p < 0.01, respectively). CONCLUSIONS: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.     

Codon 54 polymorphism of the fatty acid binding protein gene and insulin resistance in the Japanese population.

AIM: To determine the relationship of the polymorphism at codon 54 of the intestinal fatty acid binding protein gene (FABP2) with insulin resistance and susceptibility to Type 2 diabetes mellitus (DM) in the Japanese population. METHODS: We evaluated the polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 150 Type 2 DM patients and 147 healthy control subjects. The frequency of alleles encoding threonine (Thr54) and alanine (Ala54) at codon 54 of FABP2 in Type 2 DM patients was compared with that of healthy controls. Insulin sensitivity was assessed by the hyperinsulinaemic euglycaemic clamp in Type 2 DM patients with Ala54 homozygotes, Ala54/Thr54 heterozygotes and Thr54 homozygotes and by homeostasis model assessment (HOMA) in the nondiabetic group. RESULTS: The frequency of alleles encoding Ala54 and Thr54 was 0.59 and 0.41 in Type 2 DM patients, respectively, similar to that observed in nondiabetic controls (0.64 for Ala54 and 0.36 for Thr54). Insulin sensitivity was not significantly different between subjects with and without Thr54 allele either within the DM group or healthy controls. CONCLUSIONS: The allele encoding threonine in the FABP2 does not predispose to Type 2 DM or insulin resistance in the Japanese population.     

Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III genes are associated with the metabolic syndrome and dyslipidemia in a South Indian population

The Chennai Urban Population Study investigates a South Indian population with a high prevalence of cardiovascular disease associated with the metabolic syndrome (MS). The Ala54Thr polymorphism in the fatty acid-binding protein 2 (FABP2) gene as well as the T-455C and C-482T polymorphisms in the apolipoprotein C-III (APOC3) gene promoter have been associated with features of the MS in specific populations. This study evaluates in Asian-Indians the association between these polymorphisms with MS and dyslipidemia, defined according to National Cholesterol Education Program Adult Treatment Panel III. Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C. The polymorphisms were in agreement with Hardy-Weinberg equilibrium. Controls carrying FABP2 Thr54 were more likely to have MS than noncarriers (Fisher's exact test P = 0.031; odds ratio = 6.9 with a 95% confidence interval of 1.1, 43.9). Those carrying at least one polymorphic allele in both genes had a higher likelihood of having MS than wild type (Fisher's exact test P = 0.003; odds ratio = 12.1 with a 95% confidence interval of 1.88, 77.6). Dyslipidemia was associated with the polymorphism as well. The polymorphisms were not associated with MS in patients with diabetes. The association of the polymorphisms with MS and dyslipidemia could contribute to the high cardiovascular disease prevalence in this population.     

Effect of obesity on early morbidity and mortality following cardiac surgery

BACKGROUND: The prevalence of obesity in most developed nations, including Australia, continues to rise and represent an increasing public health concern. Obesity has been considered a major risk factor in patients undergoing cardiac and other major surgery. METHODS: We retrospectively analysed prospectively collected data of consecutive patients undergoing cardiac surgery between June 2001 and February 2006 at two Australian public hospitals. Patients were divided into three groups by body mass index (BMI): non-obese (BMI 20-30), obese (BMI>30-40) and morbidly obese (BMI>40). Associations between early mortality and morbidity and obesity were assessed by univariate and multivariate methods. RESULTS: Out of 4053 patients, 85 were excluded for BMI<20. A total of 2743 patients were defined as non-obese, 1136 obese and 89 morbidly obese. There were no significant differences in operative mortality, stroke, pneumonia, new renal failure, atrial fibrillation, prolonged ventilation, reintubation, readmission to intensive care, prolonged length of hospital stay or readmission within 30 days. The morbidly obese group had increased rates of deep sternal infection by univariate (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.1-19.1, p<0.001) and multivariate (OR 13.1, CI 3.4-50.7, p<0.001) analysis. The obese group had a lower rate of re-operation for bleeding by univariate (OR 0.61, CI 0.41-0.91, p=0.01) and multivariate (OR 0.64, CI 0.42-0.99, p=0.04) analysis. CONCLUSION: Apart from an increased rate of deep sternal wound infection, obesity is not associated with early mortality or other post-operative complications. The protective effect of obesity on re-operation for bleeding requires further study.     

Association between Ala54Thr substitution of the fatty acid-binding protein 2 gene with insulin resistance and intra-abdominal fat thickness in Japanese men

Summary Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 ± 8.8 years (mean ± SD) with a body mass index of 24.4 ± 3.0 kg/m². The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index. However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral fat accumulation might be involved in the impaired insulin action associated with the substitution. [Diabetologia (1997) 40: 706–710] Received: 30 December 1996 and in revised form: 10 March 1997     

A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity

OBJECTIVE: Peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) is an important regulator of adipose tissue metabolism and insulin sensitivity. The aim of this investigation was to determine whether a PPAR gamma 2 Pro12Ala polymorphism was associated with cardiovascular risk factors (obesity, blood pressure, diabetes and blood lipids) in Western Australian Caucasians (n=663). DESIGN: Subjects were selected from two population studies (the Carotid Ultrasound Disease Assessment Study (CUDAS) and Busselton Population Health Survey) on the basis of body mass index (BMI). 292 obese (BMI > or =30 kg/m) and 371 lean (BMI <25 kg /m) subjects were studied. METHODS: Blood pressure and anthropometric measurements were collected from all participants, as well as a fasting venous blood sample. Biochemical measurements (high-density lipoprotein (HDL)- and low-density lipoprotein-cholesterol, triglycerides) and PPAR gamma 2 Pro12Ala genotype were also determined. RESULTS: Obese Pro/Ala and Ala/Ala subjects had lower levels of HDL-cholesterol (P=0.032) and a trend towards higher levels of triglycerides (P=0.055) compared with obese Pro/Pro subjects. In the obese group, the Ala allele was significantly associated with the presence of combined hyperlipidaemia (odds ratio = 2.33, P=0.042). There was no significant difference in the frequency of the polymorphism between lean and obese groups (P=0.069). No association was observed between Pro12Ala genotype and obesity, blood pressure or diabetes in either group. CONCLUSIONS: Obese carriers of the Pro12Ala polymorphism have a greater risk of developing combined hyperlipidaemia, possibly due to impaired activation of PPAR gamma target genes. The Pro12Ala polymorphism is not directly associated with obesity, hypertension or diabetes in this population.     

The effect of polymorphism in the intestinal fatty acid-binding protein 2 gene on fat metabolism is associated with gender and obesity amongst non-diabetic Japanese-Americans

Aim:  The role of the codon 54 polymorphism of the fatty acid-binding protein 2 (FABP2) gene on fat metabolism has been controversial. Assuming that the effects of the polymorphism were modulated by gender and obesity which were related to lipid and glucose metabolism, we investigated this polymorphism and its effect on fat metabolism according to such factors.
Methods:  Subjects were Japanese–Americans (123 men and 126 women) who were diagnosed as non-diabetic by a 75 g oral glucose tolerance test at the baseline.
Results:  During approximately 7.8 years, 49 (24 men and 25 women) were diagnosed with type 2 diabetes. In a Cox proportional hazards model, this polymorphism was not a significant variable in the incidence of diabetes in either gender. Amongst non-obese men with the Thr54 allele, there was a significant elevation of triglycerides (TGs) (p = 0.033) compared with alanine (Ala) homozygotes. Women with the Thr54 allele had significantly elevated total cholesterol (p = 0.033) and low-density lipoprotein-cholesterol (LDL-C) (p = 0.023) compared with Ala54 homozygotes.
Conclusions:  These results therefore suggested that the effects of the FABP2 polymorphism on TG, LDL-C and body mass index were associated with gender difference and obesity amongst non-diabetic Japanese–American subjects.     

Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene V115F (G-->T) polymorphism is associated with phenotypes of metabolic syndrome in Japanese men

Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) regulates energy expenditure in the adipose tissue and is implicated in the development of obesity. A single nucleotide polymorphism in the CIDEA gene that causes an amino acid substitution of valine 115 to c(V115F) has recently been shown to be associated with obesity in the Swedish population. Here, we determined the effects of this polymorphism on phenotypes of metabolic syndrome within the Japanese population. Two hundred seventy unrelated Japanese male workers (mean age, 44.5 years) were analyzed in a cross-sectional study. The clinical features regarding metabolic syndrome, as well as CIDEA V115F polymorphism, were determined for each individual. The V115F polymorphism associated with waist circumference and fasting plasma glucose. These parameters were at higher levels in the VF + FF group than in the VV group (P < .05). The VF + FF group compared with the VV group had a higher prevalence for abdominal obesity (odds ratio [OR] = 1.89; 95% confidence interval [CI], 1.03-3.44), high fasting plasma glucose (OR = 2.81; 95% CI, 1.03-7.67), and metabolic syndrome (OR = 3.15; 95% CI, 1.05-9.48). These results suggest that the F allele of the CIDEA gene may serve as a risk factor for phenotypes related to metabolic syndrome in Japanese men.     

Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity

Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro(39)Pro and Ile(178)Ile) and three nonsynonymous variants (Ala(242)Ser, Arg(517)Cys, and Gly(532)Val). Furthermore, the rare Ala(242)Ser was identified in two families and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and Arg(517)Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.     

Morbid obesity in the medical ICU.

Study objective: To describe the clinical course, complications, and prognostic factors of morbidly obese patients admitted to the ICU compared to a control group of nonobese patients. DESIGN: A retrospective study. SETTING: Two university-affiliated hospitals. METHODS: We reviewed the medical records of 117 morbidly obese patients (body mass index >/= 40 kg/m(2)) admitted to the medical ICU between January 1994 and June 2000. Data collected included demographic information, comorbid condition, APACHE (acute physiology and chronic health evaluation) II score, invasive procedures, organ failure, and in-hospital mortality. RESULTS: Obstructive airway disease, pneumonia, and sepsis were the main reasons for admission to the ICU in the morbidly obese group. Sixty-one percent of the morbidly obese patients and 46% of the nonobese group required mechanical ventilation (p = 0.02). The mean lengths of mechanical ventilation and ICU stay were significantly longer for the morbidly obese group (7.7 +/- 9.6 days and 9.3 +/- 10.5 days vs 4.6 +/- 7.1 days and 5.8 +/- 8.2 days, respectively; p < 0.001). APACHE II scores were not significantly different in the two groups (19.1 +/- 7.6 and 20.6 +/- 12.2; p = 0.6). Overall mortality was 30% for the morbidly obese patients and 17% for the nonobese group (p = 0.019). By multivariate analysis, multiorgan failure (odds ratio [OR], 4.6; 95% confidence interval [CI], 2.1 to 16.6), PaO(2)/fraction of inspired oxygen < 200 for > 48 h (OR, 2.3; 95% CI, 1.2 to 7.8), and depressed left ventricular ejection fraction < 40% (OR, 1.4; 95% CI, 1.03 to 13.8) were independently associated with ICU mortality in the morbidly obese group. CONCLUSION: We conclude that critically ill morbidly obese patients are at increased risk of morbidity and mortality compared to the nonobese patients.     

Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men

The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid binding protein 2 (FABP2) gene has been reported to be associated with increased fat oxidation and insulin resistance in several populations. It has been hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of fatty acids and thereby an impairment of insulin action, but this hypothesis has not been proven in vivo. We studied the association between the Ala54Thr polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well as basal insulin level, basal metabolic rate, and fat oxidation rate in 96 healthy young Korean men. Among our subjects, the allele frequency of the Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to have a higher mean fasting plasma insulin concentration and a higher basal fat oxidation rate compared with the subjects who were homozygous for the Ala54-encoding allele. However, there was no significant difference in basal metabolic rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism. These results suggest that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and hyperinsulinemia in normal Korean men, but these effects are not mediated by an increase in the intestinal fatty acid absorption.     

Ala92 type 2 deiodinase allele increases risk for the development of hypertension

Accumulating evidence suggests that genes of the hypothalamic-pituitary-thyroid pathway influence susceptibility to hypertension. Type 2 iodothyronine deiodinase is responsible for the conversion of thyroxine to tri-iodothyronine for use in peripheral tissues. The present study evaluated whether a type 2 iodothyronine deiodinase nonsynonymous polymorphism, threonine 92 to alanine (Thr92Ala), is a determinant of hypertension susceptibility. A total of 372 euthyroid subjects were genotyped for Thr92Ala polymorphism using the Sequenom MassARRAY platform. Associations with hypertension and hypertension-related intermediate phenotypes were performed with generalized estimating equations. Type 2 iodothyronine deiodinase Thr92Ala allele frequencies differed significantly between hypertensive and normotensive subjects, with an excess of Ala92 carriers in hypertensive compared with normotensive subjects (64.8% versus 47.1%; P=0.011). Adjusted for age, gender and race, the estimated odds ratio for hypertension in Ala92 allele carriers compared with Thr92 homozygotes was 2.11 (95% CI: 1.15 to 3.89). Among euthyroid adults, the common Ala92 allele of the type 2 iodothyronine deiodinase increases risk for the development of hypertension. These data support an important role for genetic variation in the hypothalamic-pituitary-thyroid pathway in influencing susceptibility to hypertension.     

Association of genetic polymorphisms in the fibrinogen and platelet glycoprotein genes with unstable angina in Chinese patients

BACKGROUND: Inherited predisposition has been associated with coronary artery disease (CAD) in the white population. HYPOTHESIS: The objective of this study was to investigate the association between the risk of unstable angina (UA) and genetic factors believed to be associated with an increased tendency toward thrombosis (the variable number of tandem repeats [VNTR] polymorphism of the platelet glycoprotein [GP] Ib alpha gene, Pl(A1/A2) of the platelet GP IIIa gene, 448G/A of the Bbeta fibrinogen gene and Thr312Ala of the Aalpha fibrinogen gene) in Chinese patients with UA. METHODS: We performed a case/control study evaluating 69 Chinese patients (43 men, 26 women) with UA and 69 control subjects without CAD, individually matched for age and gender. The restriction fragment length polymorphism (RFLP) method was used to determine the genetic polymorphisms. RESULTS: The frequencies of GP Ib alpha C/B genotype and Bbeta fibrinogen 448A allele were higher in patients with UA (46.4 vs. 30.4%, odds ratio [OR] 1.977, 95% confidence interval [CI] 0.98-3.97, p = 0.054, and 49.3 vs. 20.3%, OR 3.816, 95% CI 1.797-8.103, p = 0.000, respectively). Only four subjects (two cases, two controls) with GP IIIa Pl(A2) allele were found, and there was no association between Aalpha fibrinogen Thr312Ala polymorphism and UA. CONCLUSIONS: Chinese patients with UA had increased frequencies of GP Ib alpha C/B genotype and Bbeta fibrinogen 448A allele. These data suggest that some genetic factors may influence the development of UA.     

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

BACKGROUND: Gut hormones and their receptors are considered important in the control of feeding behavior. The gut hormone peptide-YY (PYY) has anorexic effects via the inhibitory neuropeptide Y2 receptor (Y2R) highly expressed in orexigenic NPY/AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. DESIGN: Genetic case-control association study of single nucleotide polymorphisms (SNPs) in Y2R and PYY. SUBJECTS: Swedish Caucasians comprising 148 lean, 129 overweight/obese and 226 morbidly obese men.Measurements:Genotypes of the common, silent and conserved SNP Y2R 585T>C and the common SNP PYY Arg72Thr, as well as various obesity-related clinical parameters.Results:Obese men had a lower allele and homozygosity frequency of the common allele 585T>C:T which was particularly evident comparing morbidly obese with lean men (P = 0.002), and analyzing dependence between continuous body mass index (BMI) and genotype (P = 0.002). In agreement, systolic blood pressure tended to be lower in those homozygous for allele T, which was not explained by the BMI - genotype dependence. We found no association to obesity for the PYY Arg72Thr polymorphism, which is located nearby the essential carboxy terminal. CONCLUSION: A common and conserved variant of the PYY and NPY receptor Y2R is less prevalent among obese compared to among lean Swedish men. This suggests that the common Y2R variant is protective against obesity. Our findings further implicate Y2R in food intake regulation.