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Jodi A Flaws - One of the best experts on this subject based on the ideXlab platform.

  • tumor necrosis factor tnf receptor type 2 is an important mediator of tnf alpha function in the mouse ovary
    Biology of Reproduction, 2007
    Co-Authors: Chuck R Greenfeld, Katherine F Roby, Melissa E Pepling, Janice K Babus, Paul F Terranova, Jodi A Flaws
    Abstract:

    Abstract It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. TNFRSF1B deletion led to an apparent accele...

  • tumor necrosis factor tnf receptor type 2 is an important mediator of tnf alpha function in the mouse ovary
    Biology of Reproduction, 2007
    Co-Authors: Chuck R Greenfeld, Katherine F Roby, Melissa E Pepling, Janice K Babus, Paul F Terranova, Jodi A Flaws
    Abstract:

    It is believed that a finite pool of primordial follicles is established during embryonic and neonatal life. At birth, the mouse ovary consists of clusters of interconnected oocytes surrounded by pregranulosa cells. Shortly after birth these structures, termed germ cell cysts or nests (GCN), break down to facilitate primordial follicle formation. Tumor necrosis factor alpha (TNF) is a widely expressed protein with myriad functions. TNF is expressed in the ovary and may regulate GCN breakdown in rats. We investigated whether it participates in GCN breakdown and follicle formation in mice by using an in vitro ovary culture system as well as mutant animal models. We found that TNF and both receptors (TNFRSF1A and TNFRSF1B) are expressed in neonatal mouse ovaries and that TNF promotes oocyte death in neonatal ovaries in vitro. However, deletion of either receptor did not affect follicle endowment, suggesting that TNF does not regulate GCN breakdown in vivo. TNFRSF1B deletion led to an apparent acceleration of follicular growth and a concomitant expansion of the primordial follicle population. This expansion of the primordial follicle population does not appear to be due to decreased primordial follicle atresia, although this cannot be ruled out completely. This study demonstrates that mouse oocytes express both TNF receptors and are sensitive to TNF-induced death. Additionally, TNFRSF1B is demonstrated to be an important mediator of TNF function in the mouse ovary and an important regulator of folliculogenesis.

Akiko Kuwahara - One of the best experts on this subject based on the ideXlab platform.

  • TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma
    Journal of experimental & clinical cancer research : CR, 2010
    Co-Authors: Akiko Kuwahara, Motohiro Yamamori, Megumi Fujita, Tatsuya Okuno, Takao Tamura, Kaori Kadoyama, Noboru Okamura, Tsutomu Nakamura, Toshiyuki Sakaeda
    Abstract:

    Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -α and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed. Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor TNFRSF1B gene were determined by a TaqMan® MGB probe-based polymerase chain reaction. The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors. Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.

  • TNFRSF1B a1466g genotype is predictive of clinical efficacy after treatment with a definitive 5 fluorouracil cisplatin based chemoradiotherapy in japanese patients with esophageal squamous cell carcinoma
    Journal of Experimental & Clinical Cancer Research, 2010
    Co-Authors: Akiko Kuwahara, Motohiro Yamamori, Megumi Fujita, Tatsuya Okuno, Takao Tamura, Kaori Kadoyama
    Abstract:

    Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -α and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed. Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor TNFRSF1B gene were determined by a TaqMan® MGB probe-based polymerase chain reaction. The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors. Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.

Motohiro Yamamori - One of the best experts on this subject based on the ideXlab platform.

  • TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma
    Journal of experimental & clinical cancer research : CR, 2010
    Co-Authors: Akiko Kuwahara, Motohiro Yamamori, Megumi Fujita, Tatsuya Okuno, Takao Tamura, Kaori Kadoyama, Noboru Okamura, Tsutomu Nakamura, Toshiyuki Sakaeda
    Abstract:

    Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -α and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed. Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor TNFRSF1B gene were determined by a TaqMan® MGB probe-based polymerase chain reaction. The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors. Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.

  • TNFRSF1B a1466g genotype is predictive of clinical efficacy after treatment with a definitive 5 fluorouracil cisplatin based chemoradiotherapy in japanese patients with esophageal squamous cell carcinoma
    Journal of Experimental & Clinical Cancer Research, 2010
    Co-Authors: Akiko Kuwahara, Motohiro Yamamori, Megumi Fujita, Tatsuya Okuno, Takao Tamura, Kaori Kadoyama
    Abstract:

    Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -α and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed. Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor TNFRSF1B gene were determined by a TaqMan® MGB probe-based polymerase chain reaction. The genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors. Genetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.

Stuart H. Ralston - One of the best experts on this subject based on the ideXlab platform.

  • Association between TNFRSF1B polymorphisms and bone mineral density, bone loss and fracture.
    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteopor, 2004
    Co-Authors: Paul N. Tasker, Omar M. E. Albagha, Clifford B. Masson, David M. Reid, Stuart H. Ralston
    Abstract:

    The TNFRSF1B gene, which encodes the p75 TNF receptor, is a strong functional and positional candidate gene for susceptibility to osteoporosis. In a previous study, we reported that polymorphic variation in the 3’ untranslated region of TNFRSF1B was associated with femoral neck bone mineral density (BMD) in a population-based cohort of Scottish women. In order to further explore the role of TNFRSF1B as a candidate gene for osteoporosis, we have now studied the relationship between a promoter polymorphism in the TNFRSF1B gene and BMD, and determined whether this polymorphism interacts with other polymorphisms in TNFRSF1B to regulate bone mass, bone loss, and osteoporotic fracture. Analysis of individual polymorphisms showed weak associations between the G593A, T598G and T620C polymorphisms and femoral neck BMD (P=0.05–0.017). On haplotype analysis, the only significant association we observed was with FN BMD when haplotypes were grouped according to presence or absence of A593-T598-C620 alleles in the 3’ UTR (0.897±0.005 versus 0.841±0.01; P

  • association between TNFRSF1B polymorphisms and bone mineral density bone loss and fracture
    Osteoporosis International, 2004
    Co-Authors: Paul N. Tasker, Omar M. E. Albagha, Clifford B. Masson, David M. Reid, Stuart H. Ralston
    Abstract:

    The TNFRSF1B gene, which encodes the p75 TNF receptor, is a strong functional and positional candidate gene for susceptibility to osteoporosis. In a previous study, we reported that polymorphic variation in the 3’ untranslated region of TNFRSF1B was associated with femoral neck bone mineral density (BMD) in a population-based cohort of Scottish women. In order to further explore the role of TNFRSF1B as a candidate gene for osteoporosis, we have now studied the relationship between a promoter polymorphism in the TNFRSF1B gene and BMD, and determined whether this polymorphism interacts with other polymorphisms in TNFRSF1B to regulate bone mass, bone loss, and osteoporotic fracture. Analysis of individual polymorphisms showed weak associations between the G593A, T598G and T620C polymorphisms and femoral neck BMD (P=0.05–0.017). On haplotype analysis, the only significant association we observed was with FN BMD when haplotypes were grouped according to presence or absence of A593-T598-C620 alleles in the 3’ UTR (0.897±0.005 versus 0.841±0.01; P<0.0001). These data show that allelic variation within the TNFRSF1B gene contributes to the genetic regulation of FN-BMD and show that it is the ATC haplotype in the 3’UTR region of the gene, rather than other polymorphic variants, that seem to be responsible for the effects observed.

  • Linkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their association with bone mass in perimenopausal women.
    Human molecular genetics, 2002
    Co-Authors: Omar M. E. Albagha, Paul N. Tasker, David M. Reid, Fiona E. Mcguigan, Stuart H. Ralston
    Abstract:

    Osteoporosis is a multifactorial disease with a strong genetic component characterized by reduced bone density and increased fracture risk. A candidate locus for regulation of hip bone mineral density (BMD) has been identified on chromosome 1p36 by linkage analysis. One of the positional and functional candidate genes located within this region is the tumour necrosis factor receptor superfamily member 1B (TNFRSF1B). In order to investigate whether allelic variation in TNFRSF1B contributes to regulation of bone mass, we studied several polymorphisms of this gene in a population based cohort study of 1240 perimenopausal women from the UK. We studied a T676G change in exon 6 (196: Met-Arg) and three SNPs (G593A, T598G, and T620C) in the 3'UTR of the gene. The 3'UTR SNPs were in strong linkage disequilibrium (LD) with each other (P

  • linkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their association with bone mass in perimenopausal women
    Human Molecular Genetics, 2002
    Co-Authors: Omar M. E. Albagha, Paul N. Tasker, David M. Reid, Fiona E. Mcguigan, Stuart H. Ralston
    Abstract:

    Osteoporosis is a multifactorial disease with a strong genetic component characterized by reduced bone density and increased fracture risk. A candidate locus for regulation of hip bone mineral density (BMD) has been identified on chromosome 1p36 by linkage analysis. One of the positional and functional candidate genes located within this region is the tumour necrosis factor receptor superfamily member 1B (TNFRSF1B). In order to investigate whether allelic variation in TNFRSF1B contributes to regulation of bone mass, we studied several polymorphisms of this gene in a population based cohort study of 1240 perimenopausal women from the UK. We studied a T676G change in exon 6 (196: Met-Arg) and three SNPs (G593A, T598G, and T620C) in the 3'UTR of the gene. The 3'UTR SNPs were in strong linkage disequilibrium (LD) with each other (P<0.00001), and the exon 6 SNP was in LD with G593A and T598G (P<0.00001). We found no association between T676G alleles and BMD at the spine or hip. However, haplotype analysis showed that subjects homozygous for the A593-T598-C620 haplotype (n=85) had femoral neck BMD values 5.7% lower than those who did not carry the haplotype (n=1155; P<0.00008) and this remained significant after correcting for confounding factors and multiple testing (P<0.0009). Regression analysis showed that the ATC haplotype accounted for 1.2% of the population variance in hip BMD and was the second strongest predictor after body weight. In summary, our work supports the view that allelic variation in the 3'UTR of TNFRSF1B gene contributes to the genetic regulation of bone mass, with effects that are specific for femoral neck BMD.

Brian J Morris - One of the best experts on this subject based on the ideXlab platform.

  • tumor necrosis factor receptor 2 gene TNFRSF1B in genetic basis of coronary artery disease
    Journal of Molecular Medicine, 2001
    Co-Authors: Adam V Benjafield, Xing Li Wang, Brian J Morris
    Abstract:

    Tumor necrosis factor (TNF)-α has been implicated in pathophysiological processes in coronary artery disease (CAD). TNF receptor 2 is of particular interest in mediating such effects. The gene for this receptor (TNFRSF1B) has, moreover, been implicated in hypertension, elevated cholesterol and insulin resistance. TNFRSF1B is thus a worthy candidate in studies of the genetic basis of CAD. We therefore conducted a case-control study of a microsatellite marker with five alleles (CA13-CA17) in intron 4 of TNFRSF1B in 1006 well-characterized white patients with angiographically confirmed CAD and a control group of 183 healthy subjects. We found a strong association of the TNFRSF1B marker with CAD (χ2=40, P=0.00000069). The frequency of the CA16 allele was 33% in CAD vs. 21% in control (odds ratio, OR, to have CAD for presence vs. absence of CA16 allele in CA16 homozygotes was 4.5, 95% CI 2.1–9.4, P<0.0001; in CA16 heterozygotes or was 1.3, 95% CI 0.94–1.89, P=0.10). The frequency of the major allele (CA15) was 43% in CAD vs. 56% in controls (in CA15 homozygotes OR 0.33, 95% CI 0.20–0.52, P<0.0001; in heterozygotes OR 0.41, 95% CI 0.26–0.63, P<0.0001). In a stepwise logistic regression model the CA16 allele was significantly associated with overweight (OR 1.44, 95% CI 1.0–1.9, P=0.027). Apolipoprotein A-I was elevated (P<0.0001), as was high-density lipoprotein (P=0.098), and severity of angina was decreased (P=0.024) as a function of genotype. Plasma soluble (s) TNF-R2 was 5.1±0.1 ng/ml in CAD vs. 3.2±0.1 in control (P<0.0001), 5.2±0.1 in the presence vs. 4.6±0.2 in the absence of vessel disease (P=0.009), and rose with increasing severity of angina: 4.2±0.2 (no angina), 5.0±0.1 (stable angina), 5.4±0.2 (unstable angina; P=0.003). sTNF-R2 was correlated with age, cholesterol, creatinine, fibrinogen, transforming growth factor β and homocysteine and was influenced by TNFRSF1B genotype. Thus genetic variation in or near the TNFRSF1B locus may predispose to CAD.

  • TNFRSF1B in Genetic Predisposition to Clinical Neuropathy and Effect on HDL Cholesterol and Glycosylated Hemoglobin in Type 2 Diabetes
    Diabetes care, 2001
    Co-Authors: Adam V Benjafield, Xing Li Wang, Cheryl L. Glenn, Stephen Colagiuri, Brian J Morris
    Abstract:

    OBJECTIVE —Genetic variation in the tumor necrosis factor (TNF) receptor 2 gene ( TNFRSF1B ) has shown association with insulin resistance in type 2 diabetes, hypercholesterolemia, coronary artery disease, and essential hypertension. Here we tested the TNFRSF1B marker used in the latter studies in type 2 diabetes patients. RESEARCH DESIGN AND METHODS —A case-control study of a microsatellite marker with five alleles ( CA13 – CA17 ) in intron 4 of TNFRSF1B was performed in 357 well-characterized white patients and 183 healthy control subjects. RESULTS —The CA16 allele was associated with clinical neuropathy (frequency = 27% in 69 patients with the condition versus 16% in 230 subjects without the condition; χ 2 = 9.0, P = 0.011; odds ratio = 2.1 [95% CI 1.2–3.8]). No association was seen with other complications or diabetes itself. The CA16 allele tracked with elevation plasma HDL cholesterol (1.3 ± 0.2, 1.2 ± 0.4, and 1.1 ± 0.2 for CA16/CA16 , CA16/ –, and –/–, respectively; n = 9, 110, and 218, respectively; P = 0.009) and reduction in plasma glycosylated hemoglobin (6.6 ± 0.3, 8.3 ± 0.2, and 8.1 ± 0.1 for CA16/CA16 , CA16/ –, and –/–, respectively; n = 9, 102, 205, respectively; P = 0.007). Significance remained after Bonferroni correction for multiple testing. CONCLUSIONS —Genetic variation in or near TNFRSF1B may predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased HDL cholesterol in type 2 diabetes patients. The latter could be part of a protective response.

  • Tumor necrosis factor receptor 2 gene (TNFRSF1B) in genetic basis of coronary artery disease.
    Journal of molecular medicine (Berlin Germany), 2000
    Co-Authors: Adam V Benjafield, Xing Li Wang, Brian J Morris
    Abstract:

    Tumor necrosis factor (TNF)-alpha has been implicated in pathophysiological processes in coronary artery disease (CAD). TNF receptor 2 is of particular interest in mediating such effects. The gene for this receptor (TNF-RSF1B) has, moreover, been implicated in hypertension, elevated cholesterol and insulin resistance. TNFRSF1B is thus a worthy candidate in studies of the genetic basis of CAD. We therefore conducted a case-control study of a microsatellite marker with five alleles (CA13-CA17) in intron 4 of TNFRSF1B in 1006 well-characterized white patients with angiographically confirmed CAD and a control group of 183 healthy subjects. We found a strong association of the TNFRSF1B marker with CAD (chi2=40, P=0.00000069). The frequency of the CA16 allele was 33% in CAD vs. 21% in control (odds ratio, OR, to have CAD for presence vs. absence of CA16 allele in CA16 homozygotes was 4.5, 95% CI 2.1-9.4, P

  • Linkage and association of tumor necrosis factor receptor 2 locus with hypertension, hypercholesterolemia and plasma shed receptor
    Human molecular genetics, 2000
    Co-Authors: Cheryl L. Glenn, Adam V Benjafield, William Y.s. Wang, Brian J Morris
    Abstract:

    Tumor necrosis factor (TNF) receptor 2 (TNF-R2) has been implicated in insulin resistance and metabolic syndrome disorders, one of which is hypertension (HT). We therefore decided to test markers in and near the TNF-R2 gene ( TNFRSF1B) for linkage and association with HT, as well as hypercholesterolemia, and plasma levels of the shed soluble receptor (sTNF-R2). The linkage study, which involved 200 HT Anglo-Celtic Caucasian sibpairs, indicated a sharp, significant linkage peak centered at TNFRSF1B (multipoint maximum LOD score = 2.6 and 3.1 by weighted and unweighted MAPMAKER/SIBS, respectively; two-point LOD scores = 2.9 and 3.9 by weighted and unweighted SPLINK, respectively; P = 10 –4 by identical-by-state χ 2 ). The case–control study in 134 unrelated HTs who were the offspring of two HT parents and 197 normotensives (NTs) whose parents were both NTs, indicated possible association of TNFRSF1B with HT by haplotype analysis (P = 0.008). Plasma sTNF-R2 was elevated in HTs (P < 0.0001) and showed a correlation with systolic and diastolic blood pressure (BP )( P