Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Dong Hee Han; Su Kang Kim; Sungwook Kang; Bong-Keun Choe; Keon Sik Kim; Joo-Ho Chung

doi:10.4196/kjpp.2008.12.3.125

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Han, Kim, Kang, Choe, Kim, and Chung: Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Original Article

Korean J Physiol Pharmacol 2008;12(3):125-129.

Published online: 17 June 2008

DOI: https://doi.org/10.4196/kjpp.2008.12.3.125

Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Dong Hee Han^1,^∗, Su Kang Kim^1,^∗, Sungwook Kang¹, Bong-Keun Choe^1,², Keon Sik Kim³, Joo-Ho Chung¹

¹Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Korea

²Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul 130-701, Korea

³Department of Anesthesiology and Pain Medicine, School of Medicine, Kyung Hee University, Seoul 130-701, Korea

Corresponding to: Joo-Ho Chung, Kohwang Medical Research Institute, Department of Pharmacology, School of Medicine, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. (Tel) 82-2-961-0281, (Fax) 82-2-968-0560, (E-mail) flyexcel@hanmail.net, jhchung@khu.ac.kr

^∗ These first authors contributed equally to this article.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and forty two overweight/obese (BMI ≥23) and 145 normal (BMI 18 to <23) subjects were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used for the analysis of genetic data. A linkage disequilibrium (LD) block was discovered among the 5 SNPs selected, including rs17242319, rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was found to be significantly different. The results suggest that MMP2 may be associated with overweight/obese in Korean population.

Keywords: Body mass index, Linkage disequilibrium, Matrix metallopeptidase 2, Obesity, Single nucleotide polymorphism

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Fig. 1.

Gene map and linkage disequilibrium (LD) in matrix metallopeptidase 2 (MMP2) gene. (A) Gene map of single nucleotide polymorphisms (SNPs) in MMP2 on chromosome 16. Exons are marked with box. The coding region is black-boxed and untranslation regions are white-boxed. Asterisk (∗) indicates a significant SNP. Arrow indicates the location of each SNP. EX, exon. (B) LD coefficient (|D'|) and LD blocks among SNPs of MMP2. Block 1 consists of rs17242319, rs1053605, rs243849, and rs2287074.

Table 1.

Logistic regression analysis and genotype frequency of matrix metallopeptidase 2 (MMP2) polymorphisms in control and overweight/obesity subjects

SNP	Protein residue	Genotype	Control	Overweight/obesity	Codominant	p	Dominant	p	Recessive	p
Locus	Protein residue	Genotype	n=145 (%)	n=142 (%)	OR (95% CI)	p	OR (95% CI)	p	OR (95% CI)	p
rs17242319	Gly226 Gly	G/G	109 (75.2)	91 (64.1)	1.64 (1.06~2.54)	0.023	1.70 (1.02~2.82)	0.041	2.83 (0.73~10.88)	0.110
(rs1132896)		G/C	33 (22.8)	43 (30.3)
Exon 5		C/C	3 (2.1)	8 (5.6)
rs1053605	Thr250Thr	C/C	106 (73.1)	114 (80.3)	0.73 (0.43~1.22)	0.230	0.67 (0.38~1.16)	0.150	2.06 (0.18~22.94)	0.550
Exon 5		C/T	38 (26.2)	26 (18.3)
		T/T	1 (0.7)	2 (1.4)
rs243849	Asp383Asp	C/C	97 (66.9)	100 (70.4)	0.88 (0.56~1.38)	0.570	0.85 (0.52~1.40)	0.520	1.02 (0.20~5.15)	0.980
Exon 7		C/T	45 (31.0)	39 (27.5)
		T/T	3 (2.1)	3 (2.1)
rs2287074	Thr460Thr	G/G	74 (51.0)	70 (49.3)	1.08 (0.76~1.56)	0.660	1.07 (0.67~1.70)	0.770	1.23 (0.53~2.84)	0.630
Exon 9		G/A	60 (41.4)	59 (41.5)
		A/A	11 (7.6)	13 (9.2)
rs10775332	Phe602Phe	C/C	76 (52.4)	74 (52.1)	1.19 (0.80~1.76)	0.390	1.01 (0.64~1.61)	0.960	3.97 (1.08~14.56)	0.022
Exon 12		C/T	66 (45.5)	57 (40.1)
		T/T	3 (2.1)	11 (7.8)

Genotype distributions are shown as number (%). Odds ratio (OR), 95% confidence interval (CI), and p values were from logistic regression analysis with codominant, dominant, and recessive models controlling age and gender as covariates. SNP, single nucleotide polymorphism.

Table 2.

Haplotype analysis of matrix matrix metallopeptidase 2 (MMP2) polymorphisms in control and overweight/obesity subjects

	Haplotype	Freq	Control		Overweight/obesity		Chi Square	p
	Haplotype	Freq	+	−	+	−	Chi Square	p
ht1	GCCG	0.5366	155.0	135.0	152.1	131.9	0.001	0.974
ht2	GCTG	0.1633	49.8	240.2	45.0	239.0	0.183	0.669
ht3	CCCA	0.1618	37.1	252.9	55.6	228.4	4.858	0.028
ht4	GTCA	0.1083	37.0	253.0	25.2	258.8	2.259	0.133

Each haplotype with a frequency of more than 0.1 is shown. ht:haplotype. Haplotype1, 2, 3, and 4 consist of rs17242319, rs1053605, rs243849, and rs2287074. p-values of haplotype association were calculated using Haploview 3.32.

Table 3.

Genotype frequencies of matrix metallopeptidase 2 (MMP2) polymorphisms in each population

SNP	Genotype	Control	Overweight/obesity	HapMap-CEU	HapMap-HCB	HapMap-JPT
SNP	Genotype			European	Chinese	Japanese
rs17242319	G/G	0.752	0.641	0.309	0.757	0.575
(rs1132896)	G/C	0.228	0.303	0.527	0.243	0.350
	C/C	0.021	0.056	0.164	0.000	0.075
rs1053605	C/C	0.731	0.803	0.867	0.756	0.705
	C/T	0.262	0.183	0.117	0.244	0.295
	T/T	0.007	0.014	0.017	0.000	0.000
rs243849	C/C	0.669	0.704	0.767	0.600	0.667
	C/T	0.310	0.275	0.233	0.333	0.289
	T/T	0.210	0.021	0.000	0.067	0.044
rs2287074	G/G	0.510	0.493	0.254	0.511	0.432
	G/A	0.414	0.415	0.492	0.489	0.386
	A/A	0.076	0.092	0.254	0.000	0.182
rs10775332	C/C	0.524	0.521	0.200	0.578	0.467
	C/T	0.455	0.401	0.600	0.311	0.489
	T/T	0.021	0.078	0.200	0.111	0.044

From database (http://www.ncbi.nlm.nih.gov/sites/entrez).

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