Genotype of the LMNA 1908C>T variant is associated with generalized obesity in Asian Indians in North India

Objective To determine the frequency distribution of LMNA 1908C>T SNP and its association with generalized obesity, abdominal obesity and coexistent metabolic disorders in nondiabetic Asian Indians living in a metropolitan city of north India. Design A cross-sectional population-based study of LMNA 1908C>T polymorphism with obesity and insulin resistance as outcome. Patients Five hundred and fifty-one Asian Indians, with 240 obese and 289 nonobese subjects. Measurements Allelic and genotypic frequency of LMNA 1908C>T were determined by PCR-RFLP. Association of LMNA alleles and genotypes was analysed with various measures of obesity [BMI >= 25 kg/m(2), percentage body fat (by DEXA); subcutaneous and intra-abdominal fat at L2-3 level by single slice MRI in a sub-sample and surrogate marker of insulin resistance (fasting serum insulin levels >10 mu U/ml in men and >11 mu U/ml in women). Results Forty-six per cent of the subjects had generalized obesity while 54% had abdominal obesity. Frequency of C and T alleles was 0.71 and 0.29, respectively. Higher frequency of variant allele (T) was observed in obese than nonobese individuals (P = 0.001). On multivariate analysis adjusting for age, gender and serum insulin levels, subjects with LMNA1908T/T genotype were at 5.6 times higher risk [OR (95% CI): 5.6 (2.5-12.2), P = 0.001], while individuals with genotypes with at least one T allele, i.e. 1908C/T and T/T genotypes, were at 2.7 times higher odds to develop generalized obesity [OR (95% CI): 2.7 (1.8-4.1), P = 0.001]. Conclusion LMNA 1908T/T and C/T genotypes emerged as independent genetic risk factors for generalized obesity in Asian north Indians.