The Association of Human Leukocyte Antigen(HLA) Alleles and Type 2 Diabetes Mellitus (T2DM) among Mexican Americans (MA)

The epidemic of type 2 diabetes mellitus (T2DM) is ranked as a major public health priority across the United States and especially in the El Paso, Texas region. The risk for the development of T2DM is greater in minority groups, particularly among Mexican Americans (MA) who comprise approximately 78% of El Paso\u27s population. The growing incidence of T2DM in this group is typically attributed to increase in weight (obesity). The incidence of diabetes may also be influenced by genetic factors that are unique to this group. Several earlier studies have identified genetic markers for type 1 diabetes mellitus (T1DM). These markers, which reside in the major histocompatibility complex (MHC), are known as the human leukocyte antigens (HLA). These are divided into Class I (HLA-A, B, C loci) and Class II (HLA-DR and DQ loci) antigens. Although some antigens are purported to be protective, other antigens are indicated for possible susceptibility with T2DM, particularly among MA. This includes the association of Class II alleles and T2DM in this ethnic population. However, there are only a few studies that have explored the association of HLA and T2DM among MAs. Given the limited study and information available, genetic markers for susceptibility and protective effects for MA with and without T2DM would be merited. This study is guided by the following research questions: (1) What is the relationship between HLA Class I (HLA-A, B, C loci) antigens and T2DM among MA?; (2) What is the relationship between HLA Class II (HLA-DR and DQ loci) antigens and T2DM among MA?; and (3) What is the relationship between specific HLA Class II (HLA-DRB1*, DQA1*, DQB1* loci) alleles and T2DM among MA? The genetic testing proposed for this study has the potential to significantly advance our understanding of the genetic basis of T2DM. This is especially important for advancing our knowledge as it relates to MA people. Early detection of individuals with susceptibility or protective factors for T2DM will likely allow for (1) protection or delay of the onset of diabetes through known preventive strategies; (2) earlier treatment of the disease; and/or (3) prevention of chronic diabetes complications for those individuals. Methodology of this case-controlled study was divided into two parts: Part I of the study consisted of 110 cases (with T2DM), 196 controls #1 (without T2DM and without family history of T2DM), and 24 controls #2 (with family history and without T2DM). These groups were analyzed by serological and whenever possible confirmed by SSP-DNA methods. Sierra Medical Center Transplant Immunology Laboratory was instrumental for collection of HLA data. Part I focused on data analysis for HLA-A, B, C, DR, and DQ antigens in association with T2DM. Part II of the study involved 57 frozen samples derived from a previous study conducted at The University of Texas at El Paso. Additional testing and analysis included 22 frozen blood samples that were derived from Sierra Medical Center, El Paso, Texas. The HLA-DNA alleles testing were performed at Las Palmas Medical Center using Genomic DNA extracted from human leukocytes. Extracted DNA was used for identifying HLA DRB1*, DQA1*, DQB1* alleles. The process involved a reverse sequence-specific oligogonucleotide probes (rSSO) methodology. The testing employed in the study utilized LABType, Luminex technology that discriminates between the different alleles. Following a polymerase chain reaction (PCR) process, the amplified DNA product was biotinylated, which allows it to detect using R-Phycoerythrin-conjugated Strepavidin (SAPE). The data was analyzed using PROC LOGISTIC in the SAS Statistical Software. Logistic regression was used to calculate crude and adjusted odds ratio (OR), chi-square, and p-value with the binary outcome for T2DM. The results of the SAS analysis showed statistically significant protective and susceptible association with controls and T2DM. HLA-A3 and B35 antigens showed protective association with T2DM and control #1 (without T2DM and without history of T2DM) with crude OR and adjusted age and sex OR. The susceptible association demonstrated with T2DM and control # 1 was associated with HLA-B44, B49, B50, and C5 antigens with crude OR and/or adjusted age and sex OR. The T2DM and controls #2 (without T2DM and with family history of T2DM) indicated protective association with HLA-A2 and A25 antigens for crude OR and not with adjusted (age/sex) OR. The HLA-A28, B56, B57, and DQ1 antigens showed protective association with adjusted (age and sex) OR and not with crude OR. All these associations showed a confounding factor with age and sex with case-control #1 and case-control #2. The case-control of study HLA allelic markers analysis did not show a statistically significant protective or susceptible association with T2DM, perhaps due to a smaller sample size