INSIG2 G-102A promoter variant exhibits context-dependent effect on HDL-cholesterol levels but not on BMI in Caucasians.

The INSIG2 (INSIG2 is primarily involved in the regulation of fatty acid and cholesterol synthesis) gene is suggested to be obesity related. An INSIG2 promoter variant, G-102A, has been detected and was demonstrated to be of potential functional significance. In two cohorts of middle-aged men, the association between this variant and BMI was suggested. We sought to replicate the association between the INSIG2 G-102A variant and BMI in three large Slavonic Caucasian populations. Further, we analysed the possible effect of this variant on BMI changes in a short-time intervention study. One thousand ninety-nine males and 1368 females (population- based Czech MONICA three-year cohort), 908 females from the 3PMFs study, together with 94 overweight (BMI > 27 kg/m2) females who underwent nine weeks of dietary/exercise intervention were genotyped for the INSIG2 G-102A variant using PCR-RFLP analysis. We could not detect any association between the INSIG2 G-102A variant and BMI or WHR with or without adjusting for age and gender in any population. Neither the BMI change nor anthropometric and lipid parameter changes were affected by the INSIG2 G-102A gene variant in intervened overweight females. However, MONICA females (but not males) carrying the common GG genotype had higher plasma levels of HDL cholesterol (GG homozygotes 1.51 ± 0.36 mmol/l vs. A allele carriers 1.45 ± 0.33; P < 0.05) in both surveys. Our results indicated that the G-102A INSIG2 polymorphism has no consistent effect on BMI in general populations, but could influence HDL cholesterol in females.