Mutation Screening and Identification of a Sequence Variation in the Human OB Gene Coding Region

Considine, Robert V.; Considine, Eileen L.; Williams, Charlene J.; Nyce, Mark R.; Zhang, Peili; Opentanova, Irina; Ohannesian, Joanna P.; Kolaczynski, Jerzy W.; Bauer, Thomas; Moore, J. H.; José, F.

doi:10.1006/bbrc.1996.0473

Cited by 72 publications

(35 citation statements)

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“…This variant was not present in the corresponding sibling or in any other individual analyzed and is therefore more likely to be a neutral sequence variation than a mutant that alters leptin function. This absence of mutations is consistent with recent reports in other human populations [22][23][24][25][26] and strengthens the absence of linkage in this study. Although we cannot exclude the possibility that alterations in the promoter or regulatory regions of this gene are affected in these individuals, our data and the data from other reports indicate that the leptin locus is not significantly linked to BMI and that polymorphic variants in the coding region of the leptin gene are not seen in individuals with high BMI.…”

Section: Discussionsupporting

confidence: 94%

Genetic Markers at the Leptin ( OB ) Locus Are Not Significantly Linked to Hypertension in African Americans

Onions

Hunt²,

Rutkowski

et al. 1998

Hypertension

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Abstract-Increased body mass index (BMI) has been correlated with increased blood pressure in human populations. To examine the role of the leptin gene (OB) in essential hypertension in African Americans, we performed affected sib pair analysis on a set of 103 hypertensive African American sibships using four highly polymorphic markers at the human leptin locus. No evidence of linkage was detected between these markers and the phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI Ն85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found significant linkage for the marker D7S504 (Pϭ0.029) but not for the other markers. Significance strengthened in the overweight subset of sibships for this marker (Pϭ0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and the leptin locus did not demonstrate a statistically significant relationship. Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. These results suggest that the OB gene is not a major contributor to the phenotype of essential hypertension in African Americans, although a minor contribution to the phenotype of extreme obesity in this group cannot be ruled out. (Hypertension. 1998;31:1230-1234.)

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Section: Discussionsupporting

confidence: 94%

Genetic Markers at the Leptin ( OB ) Locus Are Not Significantly Linked to Hypertension in African Americans

Onions

Hunt²,

Rutkowski

et al. 1998

Hypertension

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“…26 However, recent studies have shown a possible linkage of extreme obesity (BMI b 35±40 kg/m 2 ) with the OB gene region 27,28 indicating a possible pathogenic role of the OB gene in these very obese subjects. This region has been linked to obesity in a study of a Quebec family, 29 showing linkage between the KELL locus and BMI.…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel missense mutations in the human OB gene

et al. 1997

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OBJECTIVE: To clone the human OB gene and to investigate if mutations in the OB gene are related to juvenile onset obesity in Caucasians. DESIGN: Case-cohort study with mutational scanning of the OB gene in an obese cohort and in a population sample of young Caucasians. SUBJECTS: An obese cohort of 156 subjects with juvenile onset obesity and a population sample of 380 healthy young Caucasians. MEASUREMENTS: Various anthropometric and biochemical measures of obesity and insulin sensitivity and single strand conformation polymorphism scanning and nucleotide sequencing. RESULTS: Analysis of the coding region of the OB gene in the 536 participants revealed that one obese subject was heterozygous for a mutation at codon Phe17Leu and one normal weight subject was heterozygous for a mutation at codon Val110Met. The phenotypes of the carriers were not different from matched non-mutation carrying subjects. CONCLUSIONS: Mutations exist in the OB gene among obese as well as lean subjects although they are rare. However, it is unlikely that mutations in the coding region of the OB gene are a common cause of juvenile onset obesity among Caucasians.

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“…high fat diets). It seems that leptin levels do not change in response to a glucose load and to mixed meals in either lean or obese individuals; only after more than 12 h of either fasting or massive oral overfeeding do leptin levels deviate from their daytime plateau to exhibit a decline or rise, respectively (Kolaczynski et al, 1996aConsidine et al, 1996b). Thus, in response to chronic overfeeding (5 weeks), leptin rises to significantly higher levels than would be expected for the increase in body mass index (BMI) and percentage of body fat .…”

Section: Regulation Of Leptin Gene Expression and Circulating Leptin mentioning

confidence: 99%

Leptin: in search of role(s) in human physiology and pathophysiology

Mantzoros

Moschos

1998

Clinical Endocrinology

186

117

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Obesity, a health problem reaching epidemic proportions in western countries, is an important risk factor for the most frequent diseases in the western world, i.e. diabetes, hypertension, cardiovascular diseases and certain types of cancer. Thus, significant research efforts have been focusing on its aetiology, prevention and treatment. The recent discovery of leptin (from the Greek word leptos: i.e. thin), the product of the ob gene (Zhang et al., 1994), has greatly advanced our understanding of body adiposity and energy balance regulation. This hormone, produced mainly by adipose tissue, conveys to the brain information about the size of energy stores and activates hypothalamic centres that regulate energy intake and expenditure (Flier, 1997). Moreover, leptin affects several neuroendocrine mechanisms and regulates multiple hypothalamicpituitary axes (Flier, 1997). The realization that adipose tissue is not simply a storage depot, but also an important endocrine gland, has created new opportunities for the investigation and, possibly, treatment of diseases such as obesity and eating disorders.In this review, we discuss the biology of leptin secretion and regulation, as well as our current knowledge of the role leptin plays in various physiological and pathophysiological states. Although most available research studies have been based on animal models, a substantial amount of information has been accumulated over the last 3 years on the role of leptin in humans. Thus, this article mainly focuses on our current knowledge about the role of leptin in human physiology and pathophysiology. Finally, some of the important unanswered questions about leptin physiology are discussed and future directions for leptin research are suggested.

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Mutation Screening and Identification of a Sequence Variation in the Human OB Gene Coding Region

Cited by 72 publications

References 0 publications

Genetic Markers at the Leptin ( OB ) Locus Are Not Significantly Linked to Hypertension in African Americans

Genetic Markers at the Leptin ( OB ) Locus Are Not Significantly Linked to Hypertension in African Americans

Identification of two novel missense mutations in the human OB gene

Leptin: in search of role(s) in human physiology and pathophysiology

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