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Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.

Dong Z, Zhao D, Yang C, Zhou J, Qian Q, Ma Y, He H, Ji H, Yang Y, Wang X, Xu X, Pang Y, Zou H, Jin L, Wang J - PLoS ONE (2015)

Bottom Line: In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT.These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009).Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies.

View Article: PubMed Central - PubMed

Affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.

ABSTRACT
Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

No MeSH data available.


Related in: MedlinePlus

Odds ratios (ORs) and 95% confidence intervals (CI) from each study about the association of the rs2544390 polymorphism and gout in Asians.A meta-analysis in fixed-effect model was used to test the association.
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pone.0131302.g001: Odds ratios (ORs) and 95% confidence intervals (CI) from each study about the association of the rs2544390 polymorphism and gout in Asians.A meta-analysis in fixed-effect model was used to test the association.

Mentions: The distributions of T allele frequency in rs2544390 showed a significant difference between the gout patients and healthy controls (0.48 in cases vs 0.42 in controls) in this Chinese population; according to Fisher's exact test, the T allele of rs2544390 exhibited an association with the risk of developing gout (OR = 1.26, P = 0.020) (Table 2). To confirm the association in Asians, a meta-analysis pooled the results of this study and two previous studies in Japanese populations with inconsistent results [16, 17]. The results demonstrated a significant association between rs2544390 and gout, with the T allele being a risk factor for the development of gout in Asians (OR = 1.13, P = 0.019) (Fig 1).


Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.

Dong Z, Zhao D, Yang C, Zhou J, Qian Q, Ma Y, He H, Ji H, Yang Y, Wang X, Xu X, Pang Y, Zou H, Jin L, Wang J - PLoS ONE (2015)

Odds ratios (ORs) and 95% confidence intervals (CI) from each study about the association of the rs2544390 polymorphism and gout in Asians.A meta-analysis in fixed-effect model was used to test the association.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493088&req=5

pone.0131302.g001: Odds ratios (ORs) and 95% confidence intervals (CI) from each study about the association of the rs2544390 polymorphism and gout in Asians.A meta-analysis in fixed-effect model was used to test the association.
Mentions: The distributions of T allele frequency in rs2544390 showed a significant difference between the gout patients and healthy controls (0.48 in cases vs 0.42 in controls) in this Chinese population; according to Fisher's exact test, the T allele of rs2544390 exhibited an association with the risk of developing gout (OR = 1.26, P = 0.020) (Table 2). To confirm the association in Asians, a meta-analysis pooled the results of this study and two previous studies in Japanese populations with inconsistent results [16, 17]. The results demonstrated a significant association between rs2544390 and gout, with the T allele being a risk factor for the development of gout in Asians (OR = 1.13, P = 0.019) (Fig 1).

Bottom Line: In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT.These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009).Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies.

View Article: PubMed Central - PubMed

Affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.

ABSTRACT
Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

No MeSH data available.


Related in: MedlinePlus