Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

Luca, María De; Chambers, Michelle M.; Casazza, Krista; Lok, Kerry H.; Hunter, Gary R.; Gower, Barbara A.; Fernández, José R.

doi:10.1186/1471-2156-9-52

Cited by 13 publications

(22 citation statements)

References 40 publications

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“…The association of rs659822 with body weight and lean tissue mass was also observed in African-American women from the same population (De Luca et al, 2008); however, the effect of rs659822 on these traits in the African-American women had opposite direction, which suggests its context dependence with respect to other genes and/or environmental factors. In the same study, LAMA5 rs659822 was also associated with HDL-cholesterol (HDL-C) levels in the Caucasian women (De Luca et al, 2008). …”

Section: Introductionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

“…By performing quantitative genetic studies in the fruit fly Drosophila melanogaster and a population-based study in a human cohort, De Luca et al (De Luca et al, 2008) recently identified LAMA5 as a potential candidate gene influencing body composition traits. They showed that Caucasian premenopausal women who were homozygous for the less frequent C-allele of the LAMA5 rs659822 polymorphism had shorter stature and lower body weight, total fat mass, and lean tissue mass than those carrying at least one T allele (De Luca et al, 2008). The association of rs659822 with body weight and lean tissue mass was also observed in African-American women from the same population (De Luca et al, 2008); however, the effect of rs659822 on these traits in the African-American women had opposite direction, which suggests its context dependence with respect to other genes and/or environmental factors.…”

Section: Introductionmentioning

confidence: 99%

“…They showed that Caucasian premenopausal women who were homozygous for the less frequent C-allele of the LAMA5 rs659822 polymorphism had shorter stature and lower body weight, total fat mass, and lean tissue mass than those carrying at least one T allele (De Luca et al, 2008). The association of rs659822 with body weight and lean tissue mass was also observed in African-American women from the same population (De Luca et al, 2008); however, the effect of rs659822 on these traits in the African-American women had opposite direction, which suggests its context dependence with respect to other genes and/or environmental factors. In the same study, LAMA5 rs659822 was also associated with HDL-cholesterol (HDL-C) levels in the Caucasian women (De Luca et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects

Luca¹,

Crocco²,

Wiener³

et al. 2011

Experimental Gerontology

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Laminins are large heterotrimeric glycoproteins found in basement membranes where they play an essential role in cell-matrix adhesion, migration, growth, and differentiation of various cell types. Previous work reported that a genetic variant located within the intron 1 of LAMA5 (rs659822) was associated with anthropometric traits and HDL-cholesterol levels in a cohort of premenopausal women. The present study aimed to investigate the effect of LAMA5 rs659822 on anthropometric traits, lipid profile, and fasting glucose levels in an Italian cohort of 667 healthy elderly subjects (aged 64–107 years). We also tested for association between these traits and the single nucleotide polymorphism (SNP) rs13043313, which was previously shown to control variation in LAMA5 transcript abundance in the liver of Caucasians. In age- and gender-adjusted linear regression analyses, we did not find association of rs13043313 with any of the traits. However, under an additive model, the minor C-allele of LAMA5 rs659822 was associated with shorter stature (p =0.007) and higher fasting glucose levels (p = 0.02). Moreover, subjects homozygous for the C-allele showed on average 6% and 10% lower total cholesterol (p = 0.034) and LDL-cholesterol (p = 0.016) levels, respectively, than those carrying at least one T allele, assuming a recessive model. Finally, in analyses stratified by age groups (age range 64–89 and 90–107 years), we found that the C-allele was additively associated with increased body weight (p = 0.018) in the age group 64–89 years, whereas no association was found in the age group 90–107 years. In conclusion, this study provides evidence that LAMA5 rs659822 regulates anthropometric and metabolic traits in elderly people. Future studies are warranted to replicate these findings in independent and larger populations and to investigate whether rs659822 is the causal variant responsible for the observed associations.

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Section: Introductionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects

Luca¹,

Crocco²,

Wiener³

et al. 2011

Experimental Gerontology

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“…Other genes identified regulate fatty acid metabolism, the citric acid cycle, oxidative phosphorylation, and apoptosis. These specific genes have been shown to be involved in some manner with obesity or body weight regulation [38,39].…”

Section: Mechanisms Implicated In Weight Regainmentioning

confidence: 99%

Weight Regain Following Intentional Weight Loss in Older Adults

Ryan

2016

Curr Nutr Rep

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Weight gain results from an imbalance of dietary intake and energy expenditure, and rates of overweight and obesity remain high in our society. Although weight loss is achievable, most subjects who participate in weight loss studies will regain weight and consequently recidivism remains a problem. The effectiveness of maintenance therapy is a continuing area of investigation as various dietary, behavioral, and physical activity strategies are either being investigated or are recommended. This chapter will also introduce mechanisms proposed for weight regain after intentional weight loss and the influence of weight regain on metabolic risk in adults.

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High frequency of rare variants with a moderate-to-high predicted biological effect in protocadherin genes of extremely obese

et al. 2014

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Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic predisposition of common disorders. To investigate this for obesity, we performed exome sequencing for 30 young (mean age: 29.7 years) extremely obese Caucasian subjects (mean body mass index: 51.1 kg/m(2); m/f = 11/29). Rare variants with a moderate-to-high predicted biological effect were assembled and subjected to functional clustering analysis. It showed that the 55 clustered protocadherin genes on chromosome 5q31 have a significantly (P = 0.002) higher frequency of rare variants than a set of 325 reference genes. Since the protocadherin genes are expressed in the hypothalamus, we tested another 167 genes related to the function of the hypothalamus, but in those genes, the frequency of rare variants was not different from that of the reference genes. To verify the relation of variation in the protocadherin genes with extreme obesity, we analyzed data from more than 4,000 European Americans present on the Exome Variant Server, representing a sample of the general population. The significant enrichment of rare variants in the protocadherin genes was only observed with the group of extremely obese individuals but not in the "general population", indicating an association between rare variants in the protocadherin cluster genes and extreme obesity.

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Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

Cited by 13 publications

References 40 publications

Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects

Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects

Weight Regain Following Intentional Weight Loss in Older Adults

High frequency of rare variants with a moderate-to-high predicted biological effect in protocadherin genes of extremely obese

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