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A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population.

ABSTRACT: BACKGROUND: 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 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. METHOD: A 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). RESULT: Initial 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. CONCLUSION: No 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.

SUBMITTER: Sugunan D

PROVIDER: S-EPMC2920866 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population.

Sugunan Divya D Nair Anup K AK Kumar Harish H Gopalakrishnapillai Anilkumar A

BMC medical genetics 20100730

<h4>Background</h4>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 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 biochemic ...[more]

PMID: 20673334

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Project description:Background At present, the prevalence of pregestational diabetes is 2.2% with an overall prevalence of hyperglycaemia in pregnancy of about 16.2%. Fetuses of diabetic mothers are at risk of functional cardiac abnormalities without structural cardiac anomalies especially in the third trimester. The main aim of this study was to assess the association of diabetes with different fetal echocardiographic parameters. Methods A case control study comprising a total of 120 pregnant women (60 cases and 60 controls). The cases group included fetuses of mothers known to have pre-gestational type 2 diabetes (DM group) while the control group included fetuses of euglycaemic healthy pregnant women. They were examined twice at 23–24 weeks' gestation (visit 1) and followed up at 27–28 weeks’ gestation (visit 2). The Modified Myocardial Performance Index (Mod MPI) was obtained in all fetuses. Also, M-mode echocardiography was used to measure the interventricular septum thickness at diastole in a transverse four chamber view. Results There was a significant increase in Iso-volumetric contraction time (ICT) (45.4 ms ± 8.9), Iso-volumetric relaxation time (IRT) (54.7 ms ± 11.22), Interventricular septal thickness (IVST) (4.08 mm ± 0.8), aortic acceleration time (AAT) (54.16 ms ± 12.77) and MPI (0.64 ± 0.09) in the diabetic group compared to the normal control group ICT (38.5 ms ± 9.59), IRT (46.13 ms ± 10.29), IVST (3.17 mm ± 0.6), AAT (49.73 ms ± 10.68) and MPI (0.5 ± 0.1) (all P values were < 0.001). When comparing parameters assessed at both visits among diabetic patients, there was a significant increase in IVST in the second visit (4.74 ± 0.78 mm) compared to the first visit (4.08 ± 0.8 mm) (P value < 0.05). The incidence of hypertrophic cardiomyopathy (HCM) was significantly higher in diabetic patients than in the control group. This is was observed in both first and second visit (33.4% and 56.7%) (P value < 0.001). Conclusions Fetuses of diabetic pregnant females show a significant increase in MPI, decrease in E\A ratio and HCM. These alterations in cardiac functions and structure were found to be continuous throughout the period of time between the two visits. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-04969-5.

Project description:Adolescence is the most critical phase of human growth that radically alters physiology of the body and wherein any inconsistency can lead to serious health consequences in adulthood. The timing and pace at which various developmental events occur during adolescence is highly diverse and thus results in a drastic change in blood biochemistry. Monitoring the physiological levels of various biochemical measures in ample number of individuals during adolescence can call up for an early intervention in managing metabolic diseases in adulthood. Today, only a couple of studies in different populations have investigated blood biochemistry in a small number of adolescents however, there is no comprehensive biochemical data available worldwide. In view, we performed a cross-sectional study in a sizeable group of 7,618 Indian adolescents (3,333 boys and 4,285 girls) aged between 11-17 years to inspect the distribution of values of common biochemical parameters that generally prevails during adolescence and we observed that various parameters considerably follow the reported values from different populations being 3.56-6.49mmol/L (fasting glucose), 10.60-199.48pmol/L (insulin), 0.21-3.22nmol/L (C-peptide), 3.85-6.25% (HbA1c), 2.49-5.54mmol/L (total cholesterol), 1.16-3.69mmol/L (LDL), 0.78-1.85mmol/L (HDL), 0.33-2.24mmol/L (triglycerides), 3.56-11.45mmol/L (urea), 130.01-440.15?mol/L (uric acid) and 22.99-74.28?mol/L (creatinine). Barring LDL and triglycerides, all parameters differed significantly between boys and girls (p< 0.001). Highest difference was seen for uric acid (p = 1.3 x10-187) followed by C-peptide (p = 6.6 x10-89). Across all ages during adolescence, glycemic and nitrogen metabolites parameters varied markedly with gender. Amongst lipid parameters, only HDL levels were found to be significantly associated with gender following puberty (p< 0.001). All parameters except urea, differed considerably in obese and lean adolescents (p< 0.0001). The present study asserts that age, sex and BMI are the essential contributors to variability in blood biochemistry during adolescence. Our composite data on common blood biochemical measures will benefit future endeavors to define reference intervals in adolescents especially when the global availability is scarce.

Project description:IntroductionMost studies seeking common variant associations with type 2 diabetes (T2D) have focused on individuals of European ancestry. These discoveries need to be evaluated in other major ancestral groups, to understand ethnic differences in predisposition, and establish whether these contribute to variation in T2D prevalence and presentation. This study aims to establish whether common variants conferring T2D-risk in Europeans contribute to T2D-susceptibility in the South Asian population of Sri Lanka.MethodologyLead single nucleotide polymorphism (SNPs) at 37 T2D-risk loci attaining genome-wide significance in Europeans were genotyped in 878 T2D cases and 1523 normoglycaemic controls from Sri Lanka. Association testing was performed by logistic regression adjusting for age and sex and by the Cochran-Mantel-Haenszel test after stratifying according to self-identified ethnolinguistic subgroup. A weighted genetic risk score was generated to examine the combined effect of these SNPs on T2D-risk in the Sri Lankan population.ResultsOf the 36 SNPs passing quality control, sixteen showed nominal (p<0.05) association in Sri Lankan samples, fifteen of those directionally-consistent with the original signal. Overall, these association findings were robust to analyses that accounted for membership of ethnolinguistic subgroups. Overall, the odds ratios for 31 of the 36 SNPs were directionally-consistent with those observed in Europeans (p?=?3.2×10(-6)). Allelic odds ratios and risk allele frequencies in Sri Lankan subjects were not systematically different to those reported in Europeans. Genetic risk score and risk of T2D were strongly related in Sri Lankans (per allele OR 1.10 [95%CI 1.08-1.13], p?=?1.2×10(-17)).ConclusionOur data indicate that most T2D-risk variants identified in Europeans have similar effects in South Asians from Sri Lanka, and that systematic difference in common variant associations are unlikely to explain inter-ethnic differences in prevalence or presentation of T2D.

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A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population.

Publications

A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population.

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