J Med Assoc Thai 2021; 104 (9):51-64

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Exome Sequencing Identifying LRP2 Gene (rs2228171) Related Hyperuricemia in Thai Patients with Non-communicable Diseases
Makruasi N Mail, E-kobon T , Wannaiampikul S , Tanunyutthawongse C , Sangsawangchot P , Khuancharee K , Chansiri K

Background: Although genome-wide association studies have been conducted to investigate the association between genomic loci associated with urate concentrations and gout in a large population. However, there is a lack of information in the Thai population.
Objective: To identify the new genetic predisposition of hyperuricemia (HUA) and gout in non-communicable disease patients (NCDs).
Materials and Methods: A whole-genome sequencing (WGS) using the Illumina HiSeq X Ten platform (Macrogen, Korea) was performed on the genomic DNA of 4 adult men (HUA, gout, early-onset gout, and normal subjects) who selected from 250 individuals of Gout among Thai Population Study. Then the candidate gene was identified the association of HUA in Thai NCDs patients (n=550).
Results: The data set comprised 118,599 single-nucleotide variants were selected in all 4 participants. The missense Ala17Thr (G>A) GLUT9 mutation was found only in early-onset gout. The synonymous Pro1146Pro, A>G RREB1 mutation was identified in HUA and gout. WGS also identified synonymous Ile223Ile (C>T) ABCC4) and non-synonymous Ala2872Thr (G>A) LRP2 mutation in patients with HUA, early-onset gout, and gout. Because a missense of LRP2 (rs2228171) was found in the HUA subject. Thus the frequencies and association of rs2228171 in patients with HUA, hypertension, diabetes mellitus, heart disease, obesity, dyslipidemia, and stroke by using polymerase chain reaction and DNA sequencing analysis were investigated. Seventy-eight of 550 NCDs patients were selected. As result, an association between LRP2 and HUA was not found. The genotypes GA (adjusted OR 0.11, p=0.040), AA
(adjusted OR 0.05, p=0.017) were associated with hypertension. However, the effect of rs2228171 in hypertension was still controversial due to the small population.
Conclusion: Our study is the first cross-sectional study of the rs2228171 related HUA in Thai NCDs patients. Furthermore, the
study will be done to clarify the effect of rs2228171 and metabolic diseases such as hypertension.

Keywords: LRP2 rs2228171, Serum uric acid levels, Non-communicable disease, Single nucleotide polymorphism

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