Abstract
BackgroundGlucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level. It also exerts an effect on the synthesis and secretion of lipoprotein lipase, from adipocytes, important for lipid metabolism. The aim of our study was to do a case-control association analysis of common variants in GIP in association with type 2 diabetes and related biochemical parameters.MethodA total of 2000 subjects which includes 1000 (584M/416F) cases with type 2 diabetes and 1000 (470M/530F) normoglycemic control subjects belonging to Dravidian ethnicity from South India were recruited to assess the effect of single nucleotide polymorphisms (SNPs) in GIP (rs2291725, rs2291726, rs937301) on type 2 diabetes in a case-control manner. The SNPs were genotyped by using tetra primer amplification refractory mutation system-PCR (ARMS PCR). For statistical analysis, our study population was divided into sub-groups based on gender (male and female). Association analysis was carried out using chi-squared test and the comparison of biochemical parameters among the three genotypes were performed using analysis of covariance (ANCOVA).ResultInitial analysis revealed that, out of the total three SNPs selected for the present study, two SNPs namely rs2291726 and rs937301 were in complete linkage disequilibrium (LD) with each other. Therefore, only two SNPs, rs2291725 and rs2291726, were genotyped for the association studies. No significant difference in the allele frequency and genotype distribution of any of the SNPs in GIP were observed between cases and controls (P > 0.05). Analysis of biochemical parameters among the three genotypes showed a significant association of total cholesterol (P = 0.042) and low density lipoprotein (LDL) with the G allele of the SNP rs2291726 in GIP (P = 0.004), but this was observed only in the case of female subjects. However this association does not remain significant after correction for multiple testing by Bonferroni's inequality method.ConclusionNo statistically significant association was observed between any of the SNPs analysed and type 2 diabetes in our population. But the analysis of biochemical parameters indicates that the G allele in rs2291726 may be a putative risk allele for increased LDL cholesterol and further studies in other population needs to be carried out for ascertaining its role in cholesterol metabolism and subsequent cardiovascular risk.
Highlights
Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level
The analysis of biochemical parameters indicates that the G allele in rs2291726 may be a putative risk allele for increased low density lipoprotein (LDL) cholesterol and further studies in other population needs to be carried out for ascertaining its role in cholesterol metabolism and subsequent cardiovascular risk
The inclusion criteria of patients for this study were: a) clinically diagnosed as type 2 diabetes, which includes the scrutinizing of medical records for symptoms, use of any medication and measuring the fasting blood glucose levels following the guidelines of American Diabetes Association [28], b) age of onset or diagnosis should be less than 60 years, c) should not have any other metabolic diseases and d) belonging to Dravidian ethnicity
Summary
Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level. It exerts an effect on the synthesis and secretion of lipoprotein lipase, from adipocytes, important for lipid metabolism. GIP is a single 42 amino acid peptide derived from the post-translational processing of a 153 amino acid precursor [9] It is secreted predominantly by k-cells and released from the upper small intestine (duodenum and proximal jejunum) in response to nutrient ingestion, mainly glucose or fat rich meal [10,11]. This in turn activates adnenylyl cyclase, phospholipase A and extracellular kinase (ERK and MAP), as a result of which, there is a change in the cellular ion flux aiding insulin secretion from the pancreatic beta cells [13,14,15,16,17,18]
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