Association of single nucleotide polymorphisms of adiponectin and leptin genes with breast cancer.

Single nucleotide polymorphisms (SNPs) in adiponectin gene [rs1501299 (+276G/T) and rs266729 (-11377C/G)] and one SNP of leptin gene [rs7799039 (-2548G/A)] are known to influence plasma levels of adiponectin and leptin respectively. Literature is scarce on the association of adiponectin gene polymorphism rs266729 with breast cancer. The present study was taken up to study these polymorphisms and their association with breast cancer. Ninety-three patients diagnosed with malignant breast cancer were included as cases along with 186 age matched healthy controls. Adiponectin +276G/T, -11377C/G and leptin -2548G/A polymorphism were studied using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Adipokine levels in blood were measured using enzyme linked immunosorbent assay. Adiponectin +276G/T and leptin -2548G/A showed a significant increased risk for breast cancer even after adjusting for confounding variables like present age, age at menarche, age at first child birth and age at menopause. In the subset analysis, based on menopausal state, stronger association was observed between SNP in adiponectin gene +276G/T with the breast cancer in post-menopausal women after adjusting for all other variables. No association was found with adiponectin -11377C/G. No association of the gene polymorphisms with adipokine levels was observed. Also, no significant association was seen for the effect of gene-environment interaction i.e. presence of polymorphism with obesity and menopausal state for any of the SNPs studied. Adiponectin +276G/T is strongly associated with breast cancer in postmenopausal women while leptin -2548G/A polymorphisms is significantly associated with breast cancer irrespective of the menopausal state in south Indian subjects.

Correction of Hypothyroidism Leads to Change in Lean Body Mass without Altering Insulin Resistance.

BACKGROUND: Hypothyroidism is associated with insulin resistance, dyslipidemia, and abnormal body composition. This study assessed changes in body composition and insulin resistance after thyroxine (T4) replacement in overt hypothyroidism. METHODS: In this prospective longitudinal study carried out in a tertiary care center, adult nondiabetic patients with overt hypothyroidism were rendered euthyroid on T4. Anthropometry including skinfold thickness (SFT) at the triceps and subscapularis was recorded. Patients underwent testing for fasting plasma glucose, creatinine, serum insulin, T4, thyrotropin (TSH) and body composition analysis by dual-energy X-ray absorptiometry (DEXA) both before and at 2 months after restoration to the euthyroid state. RESULTS: Twenty-seven patients (20 female and 7 male) aged 35.3 ± 11.0 years (min-max: 17-59 years) with overt hypothyroidism were recruited. Serum T4 at the time of recruitment was 48.9 ± 24.6 nmol/l (normal range = 64.4-142 nmol/l). All patients had TSH ≥50 µIU/l. Following treatment, there was a mean body weight reduction of 1.7 kg (p = 0.01). Waist circumference as well as triceps and subscapularis SFT decreased significantly (p < 0.001). There was no change in fat mass (FM), percentage of fat (%FM) or bone mineral content in any of the specified regions or in the body as a whole. In contrast, mean lean body mass (LBM) decreased significantly by 0.8 kg (p < 0.01) in the trunk and 1.3 kg (p < 0.01) in the whole body. Insulin resistance and level of glycemia were not affected by treatment with T4. CONCLUSION: LBM decreases significantly without affecting FM after correction of hypothyroidism. Insulin resistance was not influenced by T4 treatment.