Young onset diabetes in Asian Indians is associated with lower measured and genetically determined beta-cell function:an INSPIRED study

Aims/hypothesis: South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored. Methods: Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan’s Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank. Results: The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24–39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353–616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively. Conclusions/interpretation: The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function

Agrobacterium-mediated rapid and efficient development of transgenics using shoot apex explants in two elite Indica rice cultivars

An efficient multiple shoot induction, plant regeneration, and subsequent genetic transformation system for two locally adapted recalcitrant indica rice cultivars ASD16 and ADT43 using shoot apex explants were established. Three different plant growth regulators (PGRs) were tested for their efficacy in forming multiple shoots from shoot apices. Thidiazuron (TDZ) (5.0 mg/L) induced the highest frequencies of multiple shoot induction compared to Benzyl Amino Purine (BAP) and Kinetin (Kin). Shoot apices cultured on MS basal medium devoid of plant growth regulators formed single shoots. All tested PGRs produced multiple shoots at concentrations higher than 3.0 mg/L. Indole-3-Acetic Acid (IAA) and Indole-3-Butyric Acid (IBA) were supplemented to media containing TDZ (5.0 mg/L) for assessing the root induction efficiencies and it was found that media devoid of growth hormones were sufficient to produce better-rooting frequencies comparatively. Among the two tested cultivars, ASD16 responded with better shooting frequencies than ADT43. Further, genetic transformation experiments were carried out with the shoot apex explants of both cultivars. The putative transgenic plants were screened and confirmed by transient GUS expression, PCR, and Southern hybridization in both T0 and T1 generations, respectively. This rapid and efficient regeneration system amenable to Agrobacterium-mediated genetic transformation from shoot apices may be used for genetic manipulation of recalcitrant indica varieties for varietal crop improvement strategies

Genetic engineering of cotton with a novel cry2AX1 gene to impart insect resistance against Helicoverpa armigera

Embryogenic calli of cotton (Coker310) were cocultivated with the Agrobacterium tumefaciens strain LBA4404 harbouring the codon-optimised, chimeric cry2AX1 gene consisting of sequences from cry2Aa and cry2Ac genes isolated from Indian strains of Bacillus thuringiensis. Forty-eight putative transgenic plants were regenerated, and PCR analysis of these plants revealed the presence of the cry2AX1 gene in 40 plants. Southern blot hybridisation analysis of selected transgenic plants confirmed stable T-DNA integration in the genome of transformed plants. The level of Cry2AX1 protein expression in PCR positive plants ranged from 4.9 to 187.5 ng g-1 of fresh tissue. A transgenic cotton event, TP31, expressing the cry2AX1 gene showed insecticidal activity of 56.66 per cent mortality against Helicoverpa armigera in detached leaf disc bioassay. These results indicate that the chimeric cry2AX1 gene expressed in transgenic cotton has insecticidal activity against H. armigera

Rapid clonal propagation and valepotriates accumulation in in vitro cultures of Valeriana jatamansi Jones, a high-value medicinal plant

Valeriana jatamansi is well known for its medicinal and ethnobotanical values. An efficient and rapid in vitro propagation system for V. jatamansi is presented. The shoot bud explants from V. jatamansi plants were cultured on Murashige and Skoog (MS) media supplemented with different concentrations of plant growth regulators (PGR’s). MS medium supplemented with 2 mg/L of benzyl amino purine (BAP) produced shoot bud regeneration. However, the proliferation rate was slow with fewer shoots. The nodal segments were excised from the in vitro plants raised on BAP (2 mg/L) and multiplied by supplementing MS medium with different PGR’s at different concentrations. Among the tested growth regulators, supplementation of 10% coconut water resulted in maximum shoot length (6 cm), shoot number (13.0), root length (7.5 cm) and root numbers (19.6). The genetic fidelity of the in vitro raised plants was confirmed by analysis with RAPD and ISSR markers. GC-MS profiling of the root extract from in vitro raised plant revealed the presence of 21 compounds including valeric acid which is commercially and pharmaceutically important. The protocol developed here will be useful in the future towards large scale commercial production of valepotriates from V. jatamansi

Influence of exogenous polyamines on somatic embryogenesis and regeneration of fresh and long-term cultures of three elite indica rice cultivars

The influence of putrescine (Put), spermidine (Spd), and spermine (Spm) on somatic embryogenesis (SE) and plant regeneration of three indica rice cultivars (ASD16, IR64, and ADT43) were evaluated since polyamines (PAs) are reported to play vital roles in SE and plant regeneration. Significant increases in the regeneration potential of the rice cultivars upon polyamine treatments were observed. Put (1.0 mM) induced the highest regeneration frequencies, somatic embryos, and shoot numbers. PAs influenced the fresh weights of the suspension cultures. Spd was found to be detrimental to cultivar ADT43 towards embryogeneicity, regeneration, and somatic embryo induction. Among the cultivars, ASD16 was found to respond superiorly to the polyamine treatment. Experiments with long-term cultures of the rice revealed that Put and Spm enhanced the regeneration potential, and the highest frequencies were recorded for ASD16 and IR64. Results indicate that PAs can be effectively used as growth modulators to achieve success in in vitro tissue and genetic manipulation studies with elite recalcitrant indica rice cultivars

<strong>Common and distinct genetic architecture of age at diagnosis of diabetes in South Indian and European populations</strong>

OBJECTIVE South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesised that studying the genomics of age of diagnosis in these populations may give insight into earlier age diagnosis of T2D among individuals of South Asian descent.  RESEARCH DESIGN AND METHODS  We conducted a meta-analysis of GWAS of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians.  RESULTS  We identified two signals near the TCF7L2 and CDKAL1 associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25·3 in TCF7L2 (rs7903146; p = 2·4 ×10-12, Beta = -0·436; SE = 0·02) and chromosome 6 p22·3 in CDKAL1 (rs9368219; p = 2·29 ×10-8; Beta = -0·053; SE=0·01) were directionally consistent across ethnic groups and present at similar frequencies, however both loci harboured additional independent signals that were only present in the South Indian Cohorts. A genome wide signal was also obtained at chromosome 10q26·12 in WDR11 (rs3011366; p = 3.255 ×10-8; Beta = 1·44; SE=0·25) specifically in the South Indian cohorts. Heritability estimates for the age diagnosis were much stronger in South Indian compared to Europeans, and a polygenic risk score was constructed using a South Indians, which explained about 2% trait variance. CONCLUSIONS  Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D.   </p