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Int J Mol Epidemiol Genet 2011;2(2):138-144

Original Article
Novel abdominal adiposity genes and the risk of type 2 diabetes: findings from
two prospective cohorts

Edwina Yeung, Lu Qi, Frank B. Hu, Cuilin Zhang

Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, Bethesda, Maryland; Departments of Nutrition & Epidemiology, Harvard School of
Public Health, Boston, Massachusetts; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and
Harvard Medical School, Boston, Massachusetts, USA.

Received December 20, 2010; accepted April 8, 2011; Epub April 15, 2011; published May 15, 2011

Abstract: Three loci were recently identified for central adiposity from a genome wide association study (MSRA [rs545854;
G/C], LYPLAL1 [rs2605100; G/A], TFAP2B [rs987237; A/G]). Central obesity is a strong risk factor for type 2 diabetes (T2D).
Therefore, we hypothesized that these single nucleotide polymorphisms (SNPs) would be associated with increased risk of
T2D and may influence circulating adipokine concentrations. Participants from two large case control studies nested in the
Nurses' Health Study (3394 women, 1245 cases) and the Health Professionals Follow-up Study (2154 men, 862 cases) were
genotyped for these SNPs. The association of these SNPs with plasma adipokine concentrations was determined among a
subgroup of women without diabetes (n=987). After adjustment for age and other risk factors of diabetes, the MSRA variant was
associated with an increased T2D risk in men only, with an adjusted OR of 1.30 (95% CI: 1.09-1.56) associated with each copy
of the variant allele.  In pooled analyses of men and women, each additional copy of the LYPLAL1 allele (G) was associated
with 9% increased T2D risk (adjusted OR 1.09; 95%CI: 0.99-1.19). No significant associations were seen with the TFAP2B
SNP with a pooled adjusted OR of 1.05 (95% CI: 0.95-1.17) per allele copy. In addition, carriers of the MSRA risk variant had
lower percent high molecular weight adiponectin (-2.1%, p=0.04). Carriers of the TFAP2B risk variant, however, had lower leptin
levels (-2.7 ng/ml, p=0.005). These findings suggest potential associations of novel central obesity genes with T2D risk and
adipokine regulation. (IJMEG1012002).

Keywords: Abdominal adiposity, genes, type 2 diabetes, TFAP2B, MSRA, LYPLAL1

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Address all correspondence to:
Cuilin Zhang & Lu Qi, Cuilin Zhang
Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development
6100 Executive Blvd, 7B03, Bethesda, MD 20892, USA.
Tel: 301-435-6917, Fax: 301-402-2084,
E-mail:
zhangcu@mail.nih.gov; luqi@hsph.harvard.edu