Association of Vitamin D Deficiency and Vitamin D Receptor Gene Polymorphisms with Type 1 Diabetes Risk: A South Indian Familial Study

INTRODUCTION: Vitamin D is a potent immune modulator and is associated with autoimmune diseases, including type 1 diabetes (T1D). The vitamin D levels and its receptor gene polymorphisms together in T1D are not yet investigated in the South Indian population. The present study focused on exploring the significance of vitamin D levels and vitamin D receptor (VDR) gene polymorphisms with the risk of developing T1D in the South Indian population. METHODS: Patients with T1D and unaffected first-degree relatives (FDRs) were included in this study. Genotyping of VDR polymorphisms at four different loci (FokI- F/f, BsmI- B/b, TaqI- T/t, and ApaI- A/a) was assessed through the amplification refractive mutation systempolymerase chain reaction method. Serum vitamin D levels were measured in 98 T1D patients and 75 age- and sex-matched siblings. RESULTS: A total of 120 patients with T1D and 214 FDRs were included. Vitamin D deficiency (VDD) was observed in a higher proportion of T1D patients than in controls (52% vs. 32%; p<0.03). The frequency of the FokI-FF genotype was significantly higher [odds ratio (OR)=1.66; p<0.03] in T1D patients conferring a susceptible association with the disease. Nevertheless, the increased frequency of heterozygous Ff genotype (OR=0.57; p<0.02) among controls may confer a protective association with T1D. Furthermore, the transmission disequilibrium test revealed over-transmission of ApaI-A (T: U=15/5; p<0.006) and BsmI-B alleles (T: U=17/5; p<0.01) and under-transmission of BsmI-b/ApaI-a/TaqI-T haplotype (T: U=5.4/14.4; p=0.04) from parents to T1D patients. DISCUSSION AND CONCLUSION: The present study concludes that VDD is the major contributing risk factor to T1D development in the South Indian population. Furthermore, the FokI-FF genotype, BsmI-B, and ApaI-A alleles were positively associated with T1D. In contrast, the FokI-Ff genotype and BsmI-b/ApaI-a/TaqI-T haplotype were negatively associated with T1D

SLC30A8 Gene rs13266634 C/T Polymorphism in Children with Type 1 Diabetes in Tamil Nadu, India

Objective:Zinc transporter 8 (ZnT8) is a multi-transmembrane protein situated in the insulin secretory granule of the islets of β-cells and is identified as a novel auto-antigen in type 1 diabetes (T1D). The gene coding for ZnT8, solute carrier family 30 member 8 (SLC30A8) is located on chromosome 8q24.11. This study aimed to identify the association of SLC30A8 rs13266634 C/T gene polymorphism with T1D in a sample of T1D children in Tamil Nadu, India.Methods:The family based study was conducted in 121 T1D patients and 214 of their family members as controls. The SLC30A8 gene rs13266634 C/T polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism.Results:No significant differences were observed in either allele (odds ratio: 0.92; confidence interval: 0.33-2.58; p=0.88) and genotype (CC: p=0.74; CT: p=0.82; TT: p=0.80) frequencies of rs13266634 C/T between T1D patients and controls. Transmission disequilibrium test has identified over-transmission of mutant T allele from parents to affected children (T: U=9:7) without statistical significance. Metaanalysis on the overall effects of rs13266634 C allele frequency was not different (p=0.10 and Pheterogeneity=0.99) in T1D patients as compared to the controls.Conclusion:The present study along with the meta-analysis does not show any substantial association of the rs13266634 C/T polymorphism with T1D development in this population

Population differentiation of Southern Indian male lineages correlates with agricultural expansions predating the caste system

Christina J. Adler, Alan Cooper, Clio S.I. Der Sarkissian and Wolfgang Haak are contributors to the Genographic ConsortiumPrevious studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that both Y chromosome and caste designation are paternally inherited, and genotyped 1,680 Y chromosomes representing 12 tribal and 19 non-tribal (caste) endogamous populations from the predominantly Dravidian-speaking Tamil Nadu state in the southernmost part of India. Tribes and castes were both characterized by an overwhelming proportion of putatively Indian autochthonous Y-chromosomal haplogroups (H-M69, F-M89, R1a1-M17, L1-M27, R2-M124, and C5-M356; 81% combined) with a shared genetic heritage dating back to the late Pleistocene (10–30 Kya), suggesting that more recent Holocene migrations from western Eurasia contributed, <20% of the male lineages. We found strong evidence for genetic structure, associated primarily with the current mode of subsistence. Coalescence analysis suggested that the social stratification was established 4–6 Kya and there was little admixture during the last 3 Kya, implying a minimal genetic impact of the Varna(caste) system from the historically-documented Brahmin migrations into the area. In contrast, the overall Y-chromosomal patterns, the time depth of population diversifications and the period of differentiation were best explained by the emergence of agricultural technology in South Asia. These results highlight the utility of detailed local genetic studies within India, without prior assumptions about the importance of Varna rank status for population grouping, to obtain new insights into the relative influences of past demographic events for the population structure of the whole of modern India.GaneshPrasad ArunKumar, David F. Soria-Hernanz, Valampuri John Kavitha, Varatharajan Santhakumari Arun, Adhikarla Syama, Kumaran Samy Ashokan, Kavandanpatti Thangaraj Gandhirajan, Koothapuli Vijayakumar, Muthuswamy Narayanan, Mariakuttikan Jayalakshmi, Janet S. Ziegle, Ajay K. Royyuru, Laxmi Parida, R. Spencer Wells, Colin Renfrew, Theodore G. Schurr, Chris Tyler Smith, Daniel E. Platt, Ramasamy Pitchappan, The Genographic Consortiu

Evaluation of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms in type 1 diabetes among South Indian population

Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Human leukocyte antigen-G (HLA-G) is a non-classical HLA-class I molecule having several immunomodulatory functions. Polymorphisms in HLA-G are associated with several autoimmune diseases including T1D. This study aims to evaluate the association of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms with T1D among the South Indian population. Methods: The study was performed in a cohort of 123 T1D patients along with their 51 siblings and 126 parents. The association and linkage of HLA-G 14bp Ins/Del and +3142 C/G polymorphisms with T1D were analysed, and transmission disequilibrium test (TDT) was performed. Results: Significantly increased frequencies of HLA-G 14bp Del/Del genotype (OR = 2.16, pc = 0.0302) and Del allele (OR = 1.71, pc = 0.0398) were observed in female patients compared to parents. Higher frequencies of DelDel/GG combined genotype (OR = 4.45, pc = 0.0049) and Del/G haplotype (OR = 2.91, pc = 0.0277) were observed in female patients compared to parents. TDT also revealed over-transmission of Del/G haplotype (25T vs 7UT; P = 0.0015) and a strong linkage disequilibrium between the studied polymorphisms. Conclusion: This familial study shows the association of HLA-G 3′UTR 14bp Ins/Del polymorphism with the risk of T1D among the South Indian population, especially in females

Description of the 31 tribal and non-tribal endogamous populations studied.

a<p>- 2001 Census, Government of India, <a href="http://censusindia.gov.in/" target="_blank">http://censusindia.gov.in/</a>.</p>b<p>-1981 Indian Census.</p>c<p>-1931 Indian Census.</p>d<p>- Estimated census size.</p>e<p>-1901 Indian Census.</p>f<p>- All Brahmin-related castes in Tamil Nadu,</p>g<p>-No information available.</p>h<p>-Population code used in PCA & MDS plots,</p>i<p>-Sanskrit is the language of scriptures and ceremonies, but populations quickly adopted local cultures and languages.</p>j<p>-Lower, Middle & Higher social ranks are self-perceived/assigned classifications.</p>k<p>-Approximate coordinates.</p><p>NTN (North Tamil Nadu),TNV (Tirunelveli).</p><p>DR (Dravidian), IE (Indo-European).</p