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Introduction: Association studies between single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) have been abundant. However, there are limited reports on copy number variations (CNVs) of beta-defensins (DEFB) gene in relation to T2DM. In this study, DEFB copy numbers were quantified in T2DM with nephropathy, T2DM without nephropathy and non-diabetic control groups to investigate its influence in chronic inflammation in Malaysian individuals. Methods: DEFB copy number in Malaysian individuals were quantified by using paralogue ratio tests (PRT) which allow direct quantification of gene copy number by using PRT107A and HSPD21 PRT primers. The copy number generated was then validated from insertion/deletion ratio measurement 5DEL (rs5889219) and two microsatellite analyses (EPEV-1 and EPEV-3). Results: DEFB copy number was found extending from 2 to 8 copies in the non-diabetic group (n=146), while in T2DM group (n=392), copy numbers were more extensive, ranging between 1 and 12 copies; with 1, 10 and 12 copies detected in T2DM with nephropathy group (n=202). Statistically, there is no significant difference in DEFB copy number between T2DM and the non-diabetic group (p=0.209) as well as between diabetic nephropathy and without nephropathy of the T2DM group (p=0.522). However, significant white blood cell (WBC) count was found between T2DM groups with and without diabetic nephropathy (p=0.000). Conclusion: Extreme DEFB copy numbers in T2DM with nephropathy group suggest future studies with bigger sample size are necessary to elucidate the true impact of CNVs of DEFB gene in promoting early onset of nephropathy in T2DM.

The indigenous groups of Sarawak that are well-known for diverse ethnicity featuring different cultures, languages and lifestyles, are among the earliest resident of Malaysian Borneo. The high survivorship of these early inhabitants had triggered an interest on their ability to develop immune or defense mechanisms towards the environment. Beta defensin is one of the well-studied adaptive immune functional gene of human. Beta defensins gene family plays a major role in innate and adaptive immune systems that are located in a cluster of at least seven genes on chromosome 8p23.1 with highly variable copy number. The ability of the indigenous people populating new settlements has been linked to their resistance or susceptibility towards certain disease which is influenced by the effectiveness of beta defensins adaptability. Hence, investigation on the distribution of beta defensins copy number variable gene in ethnics of Sarawak was conducted by investigating two microsatellite regions within the gene cluster. The result from 78 respondents comprising of the Iban, Bidayuh, Selako, Bugis and Jawa on the immediate copy number typing range from 2 to 8 copies. Interestingly, the copy numbers are not unique to the ethnics. They show a broad overview of shared copy number typing between them. All the sampled ethnics showed an agreement of copy number typing with modal copy of four based on EPEV1 and EPEV3 except for the Selako population. Pearson’s correlation shows excellent agreement between the samples with R2=1. The differences in copy number typing between populations were mostly due to genetic drift within the population. Natural selection had caused small populations to develop defence mechanisms and adaptability towards the environment. Furthermore, intercultural marriage within small populations has discouraged gene flow and limits genetic drift which later becomes a mechanism of evolution for beta defensins copy number gene. This study highlights the diversity and d