The combinatorial diversity of KIR and HLA class I allotypes in Peninsular Malaysia.

Killer cell immunoglobulin-like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune-mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under-represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+ HLA-C in the Malaysian Chinese group, caused by the low frequency of C2+ HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high-resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.

Distribution of 22 Single Nucleotide Polymorphisms in 13 Cytokine Genes in Malays, Chinese, and Indians in Peninsular Malaysia.

Introduction: Cytokines are cell signaling glycoproteins that are particularly important in immunity and inflammatory responses. Therefore, variations, such as single nucleotide polymorphisms (SNPs), in genes encoding for cytokines may have important consequences for their roles in health. Materials and Methods: A total of 222 unrelated, healthy, and un-admixed Malays (n = 97), Chinese (n = 77), and Indians (n = 48) with a median age of 30 years old (range 21-50) were typed for 22 cytokine gene SNPs: IL-1α -889 T/C, IL-1ß (-511 T/C, +3962 T/C), IL-1R pst1 1970 T/C, IL-1RA mspa1 11100 T/C, IL-4Rα +1902 G/A, IL-12 - 1188 C/A, IFN-γ +874 A/T, TGF-ß (cdn 10 C/T, cdn 25 G/C), TNF-α (-308 A/G, -238 A/G) IL-2 (+166 G/T, -330 T/G), IL-4 (-1098 T/G, -590 T/C, -33 T/C), IL-6 (-174 C/G, nt565 G/A), and IL-10 (-1082 G/A, -819 C/T, -592 A/C). This involved using well-established polymerase chain reaction procedures with sequence-specific primers and restriction fragment length polymorphism methods. Results: The majority of the screened cytokine gene SNPs are polymorphic in all three ethnicities. Exceptions include TGF-ß cdn 25 (G/C), IL-1ß +3962 (T/C), and TNF-α -238 (A/G), which were all observed to be monomorphic in Malays, Chinese and Indians. Many of the analyzed cytokine gene SNP genotypes deviated from Hardy-Weinberg equilibrium and the three ethnic study groups were all well-separated from reference Asian, African and European populations in a principal component analysis plot. Conclusion: We successfully typed 22 SNPs in 13 cytokine genes from genetic material collected from unrelated and un-admixed Malay, Chinese and Indian individuals in Peninsular Malaysia. These new cytokine gene population datasets reveal interesting contrasts with other populations.

Transfusion Medicine and Molecular Genetic Methods.

Transfusion procedures are always complicated by potential genetic mismatching between donor and recipient. Compatibility is determined by several major antigens, such as the ABO and Rhesus blood groups. Matching for other blood groups (Kell, Kidd, Duffy, and MNS), human platelet antigens, and human leukocyte antigens (HLAs) also contributes toward the successful transfusion outcomes, especially in multitransfused or highly immunized patients. All these antigens of tissue identity are highly polymorphic and thus present great challenges for finding suitable donors for transfusion patients. The ABO blood group and HLA markers are also the determinants of transplant compatibility, and mismatched antigens will cause graft rejection or graft-versus-host disease. Thus, a single and comprehensive registry covering all of the significant transfusion and transplantation antigens is expected to become an important tool in providing an efficient service capable of delivering safe blood and quickly locating matching organs/stem cells. This review article is intended as an accessible guide for physicians who care for transfusion-dependent patients. In particular, it serves to introduce the new molecular screening methods together with the biology of these systems, which underlies the tests.