LAMA5 variants associated with weight, lipids, body composition

19 August 2008

MedWire News: Variants in the human laminin α5 gene (LAMA5) are related to body weight and composition, height, and serum lipids, report scientists.

Previously Maria de Luca and colleagues from the University of Alabama at Birmingham in the USA discovered that a mutant of the drosophila gene laminin A (LanA) is associated with variable triglyceride storage, body weight, and total body protein content.

For the current study, the team extended their analysis to humans by studying three polymorphisms of the human version of LanA, known as LAMA5, in 101 European-American and 127 African-American women aged an average of 34 years who were participating in a longitudinal study of metabolism and obesity in the USA.

Three single nucleotide polymorphisms (SNPs) covering a large amount of the variation in LAMA5 were chosen for genotyping; rs659822 (T/C), rs2297588 (G/A), and rs944895 (T/C).

The researchers assessed whether any of these variants were associated with variation in body composition, weight, height, or lipid profile traits.

As reported in the journal BMC Genetics, significant associations were found in European-American women between rs659822 genotype and height, weight, total fat mass, lean tissue mass, and high-density lipoprotein (HDL) cholesterol.

More specifically, homozygotes for the rs659822 C allele had shorter stature, lower weight, reduced fat mass, and higher HDL cholesterol than those carrying the T allele.

Of note, the rs659822 C allele was also associated with higher weight and lean tissue mass in African-American women.

African-American women who were T allele homozygotes for rs944895 had lower triglycerides and HDL cholesterol than those carrying at least one C allele. No associations for this variant were seen in European Americans.

The final SNP, rs2297588, was not associated with any obesity-related or metabolic factors in study participants.

The researchers justify the use of drosophila as an initial model, explaining: "Like mammals, insects store fat as triglyceride in neutral lipid droplets that are accumulated in the fat body, the functional equivalent of both mammalian liver and white adipose tissue."

De Luca et al conclude: "Our cross-disciplinary genetic study implicates a member of the laminin gene family as a novel candidate gene affecting variation in body composition traits in natural populations.

"These observations motivate future studies in independent human populations to verify the effects of this gene," they add.

BMC Genet 2008: 9:52