ORIGINAL ARTICLE Replication of MACF1 gene variant rs2296172 with type 2 diabetes susceptibility in the Bania population group of Punjab, India Varun Sharma 1 & Itty Sethi 1 & Indu Sharma 1 & Gurvinder Singh 1,3 & Ankit Mahajan 2 & Arshia Angural 1 & A. J. S. Bhanwer 3 & Manoj K. Dhar 2 & K. K. Pandita 4 & Vinod Singh 1 & Ekta Rai 1 & Swarkar Sharma 1 Received: 22 July 2017 /Accepted: 5 December 2017 # Research Society for Study of Diabetes in India 2017 Abstract Microtubule actin cross-linking factor 1 (MACF1) gene variant rs2296172 has recently been associated with type 2 diabetes (T2D). However, this variant has never been evaluated as such in Indian populations. In the present replication study, we genotyped variant rs2296172 by Taqman allele discrimination assay in 432 individuals belonging to the Bania caste group from Punjab, India. The single-nucleotide polymorphism (SNP) was evaluated for association with T2D, in a population based candidate gene case-control association study design, by estimating odds ratio with 95% confidence interval. The SNP rs2296172 of MACF1 was found to be significantly associated with T2D (p = 0.02) and odds ratio (OR) = 1.59 (1.06–2.38) at 95% CI . We further emphasize that the Indian population as such is a conglomeration of various endogamous population groups. It is critical that such replication studies be carried out in various populations to find association of variants to T2D susceptibility and understand genetic heterogeneity. However, it is important to avoid pooling of samples to address the concern of population stratification. Keywords MACF1 (microtubule actin cross-linking factor 1) . T2D (type 2 diabetes) . Bania Introduction Type 2 diabetes (T2D) is a heterogeneous complex metabolic disorder with genetics and environmental factors playing a critical role. Around the globe, the estimated prevalence of T2D is 8.3%, which is expected to increase to 10.1% and in India alone; the number of individuals with diabetes is esti- mated to escalate from 65.1 million to 109 million by 2035 [1]. High heritability of ~ 70% in monozygotic twins and strong role of family history, i.e., approximately 70% in indi- viduals where both parents are affected than to the individuals (~ 40%) having one parent affected with T2D [2], indicates very high contribution of genetic content. Genetic association studies including studies based on recent methodologies like whole genome sequencing and exome sequencing have aided in the better understanding of this disorder and so far ~ 120 loci have been found to be associated with T2D [3]. However, these identified loci account for ~ 15% of heritability in T2D, indicating a lot more genetic content is yet to be identified [4]. It is anticipated that this uncharacterized content might be masked by complex mechanisms like population sub- structuring and genetic heterogeneity, warranting different strategies to be adopted. Such strategies are critical in highly diverse population groups like Asian Indians, which actually is a miscellany of diverse endogamous ethnic groups [5, 6]. Studies have also suggested that single-nucleotide polymor- phism (SNP) variations and their frequencies may have ethnicity-specific distributions and can influence the disease susceptibility studies [6]. Varun Sharma and Itty Sethi contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13410-017-0598-6) contains supplementary material, which is available to authorized users. * Ekta Rai ekta.rai@smvdu.ac.in * Swarkar Sharma swarkar.sharma@smvdu.ac.in 1 Human Genetics Research Group, Department of Biotechnology, Shri Mata Vaishno Devi University, Katra, J&K 182320, India 2 Department of Biotechnology, University of Jammu, Jammu 180006, India 3 Guru Nanak Dev University, Amritsar, India 4 Jammu, India International Journal of Diabetes in Developing Countries https://doi.org/10.1007/s13410-017-0598-6