Leptin polymorphism combinations influence BMI in Chinese

By Sally Robertson, B.Sc.Aug 7 2012

The presence of genetic variants in both the leptin gene (LEP) and the gene for its receptor (LEPR) may predispose Chinese individuals to obesity, report researchers.

Individually, none of the polymorphisms were associated with body weight or body mass index (BMI) in the Chinese Han population, but a combination of three variants across the two genes was associated with significantly increased body mass index (BMI).

"Our findings underscore the importance of gene‑gene interaction in the assessment of genetic influences on complex traits such as obesity," say Jin Lu (Changhai Hospital, Shanghai, China) and colleagues.

In a comparison of 230 individuals who were obese (BMI ≥25 kg/m²) and 202 gender- and age-matched healthy controls, genetic screening for a polymorphic microsatellite marker in the LEP gene and two LEPR polymorphisms Lys109Arg and Lys656Asn revealed no associations with obesity.

However, the II/II genotype of the LEP gene was associated with increased waist/hip ratio; homozygosity for the Lys allele of Lys109Arg was associated with higher systolic blood pressure in males; and the Asn/Asn genotype of Lys656Asn was significantly associated with increased triglyceride levels.

Interestingly, only individuals with a combination of the homozygous genotypes Arg/Arg, Asn/Asn, and II/II for Lys109Arg, Lys656Asn, and the LEP gene, respectively, had a significantly increased BMI. Individuals with this genotype combination had a mean BMI of 29.30 kg/m² compared with 26.91 kg/m² among those with other combinations.

"The most important finding in our study is the synergistic effect of of the LEP and LEPR gene polymorphism on BMI," say Lu et al.

Many genes that are neither necessary nor sufficient individually may act to predispose an individual to obesity when combined, they suggest.

The researchers say replication of the findings in independent cohorts and molecular function studies of the variants are needed in the future.

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