Elucidating the association of tmprss6 rs855791, rs5756504 and rs4820268 polymorphism and iron deficiency in obese adults in Malaysia

Obesity is becoming a social burden in Malaysia, and there is emerging evidence that obesity increase the risk of iron deficiency (ID) and iron deficiency anaemia (IDA). Polymorphisms such as single nucleotide polymorphisms (SNPs) in the transmembrane protease serine 6 (TMPRSS6) gene resulted in elevated hepcidin levels, which cause iron-refractory iron deficiency anaemia (IRIDA). Aside from IRIDA, previous studies have shown that there was significant association between the TMPRSS6 SNPs with haematological and biochemical parameters related to ID with or without anaemia in different clinical settings such as celiac disease and chronic kidney diseases. Unfortunately, limited study in identifying a possible relationship between TMPRSS6 SNPs and ID among obesity reported in Malaysia. However, the underlying mechanisms impacting iron metabolism dysregulation in this population is unknown. Therefore, this study aimed to identify the TMPRSS6 SNPs (rs855791, rs5756504 and rs4820268) that influence low blood and body iron status parameters in overweight and obese subjects with ID/IDA. Also, to elucidate the association between the identified SNPs with the haematological and biochemical parameters. A total of 62 overweight/obese patients were recruited from the Primary Care Medicine clinic at Pusat Pakar Perubatan UiTM, Sungai Buloh, Selangor. Anthropometric measurements (weight, height, BMI, waist, and hip circumference) were taken. Blood samples were collected to analyse the full blood count and iron profiles. The concentrations of serum hepcidin, Il-6, leptin and sTfR were measured. Genomic DNA was extracted to be used on identifying the SNPs located on the TMPRSS6 gene via rhAmp SNP genotyping assay (qRT-PCR). SPSS software was used to analyse the correlation between the identified SNPs, haematological and biochemical parameters among the studied group via Pearson correlation analysis, and One-way ANOVA. Approximately, 51.6% of overweight/obese subjects were iron deficient (case) and 48.4% were non-iron deficient (control). Significant low levels of haematological (haemoglobin, Hct, MCV, MCH and MCHC), iron profiles (SI, TS and SF), and biochemical (hepcidin and leptin) parameters were observed in the case group compared to the controls. In contrast, significant high levels of sTfR and TIBC were observed among the case compared to the controls. Genotyping analysis showed that rs855791 exhibits significant association with the incidence of ID and allele A was identified as the risk allele which significantly associated with low levels of haemoglobin, Hct, MCHC, SI, TS and hepcidin. No significant association were observed between rs4820268 and rs5756504 with the ID status. Meanwhile, among the iron deficient group, A/A carriers of rs855791 showed significantly associated with low levels of Hct and hepcidin. For rs5756504, among the case group, G/G carriers were significantly associated with low levels of hepcidin and leptin. No significant association was observed between rs4820268 with the studied parameters in both groups. To our knowledge, this is the recent findings on the TMPRSS6 gene polymorphisms in relation to ID among overweight/obese adults. Future studies on a larger sample size are warranted to further discover the functional structure of TMPRSS6 protein (MT-2) which was associated with the identified SNPs that caused ID/IDA to provide better insight on the SNP associated iron regulatory gene and disease management among overweight /obese populations.