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

Abstract

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. A cross-sectional population-based study of LMNA 1908C>T polymorphism with obesity and insulin resistance as outcome. Five hundred and fifty-one Asian Indians, with 240 obese and 289 nonobese subjects. 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 subsample and surrogate marker of insulin resistance (fasting serum insulin levels >10 μU/ml in men and >11 μU/ml in women). 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]. LMNA 1908T/T and C/T genotypes emerged as independent genetic risk factors for generalized obesity in Asian north Indians.