Three SNPs of FCRL3 and one SNP of MTMR3 are associated with immunoglobulin A nephropathy risk

PurposeImmunoglobulin A nephropathy (IgAN) is determined by a combination of multiple genetic and environmental factors, but its etiology and pathogenesis are not well understood. We aim to determine whether variations in FCRL3 and MTMR3 correlate with IgAN risk indices in Chinese Han people.MethodsEight single nucleotide polymorphisms (SNPs) of FCRL3 and MTMR3 were genotyped, and association analysis was performed. A total of 426 patients with IgAN and 498 healthy individuals, serving as the control group, were recruited for this association study.ResultsThere were significant associations between FCRL3 rs11264793 (OR = 0.78; 95 % CI = 0.63-0.98; p = 0.029), rs11264794 (OR = 0.81; 95 % CI = 0.67-0.98; p = 0.026) and rs7522061 (OR = 0.79; 95 % CI = 0.65-0.95; p = 0.012) and decreased risk of IgAN according to allele model results. Under genetic models, FCRL3 and MTMR3 were associated with the risk of IgAN. Interestingly, FCRL3 reduced the IgAN susceptibility only in females, while MTMR3 was a risk factor for IgAN only in males. In addition, FCRL3 rs11264793 and rs7522061 were significantly associated with a decreased risk of IgAN in different disease grades. Moreover, the haplotypes ACC (p = 0.02) and CTC (p = 0.017) of LD block rs11264794/rs7522061/rs11264799 in the FCRL3 gene were significantly associated with a decreased risk of IgAN.ConclusionsWe suggest that three SNPs of FCRL3 were associated with a decreased risk of IgAN, while one SNP of MTMR3 was associated with an increased risk of IgAN in Chinese Han populations. These findings may be useful in the development of early prognostics for IgAN.     

TAP1 and TAP2 polymorphism in Spanish patients with ankylosing spondylitis

OBJECTIVE: HLA-B27 is strongly associated with ankylosing spondylitis (AS); however, the association is not absolute and additional susceptibility factors in the MHC region could play a role. We studied the influence of polymorphism in the transporter associated with antigen processing (TAP) genes, including point mutations not previously analyzed. METHODS: HLA-B*27 typing and subtyping as well as TAP1 and TAP2 typing were performed by PCR-RFLP. Forty-four AS individuals were compared to 61 ethnically matched random individuals and 35 B*27-positive healthy unrelated individuals as controls. RESULTS: The frequency of the TAP1B allele was significantly greater in the patient group compared with the random controls (corrected p value (p(c)) = 0.035; odds ratio = 15.8, p = 0.01). A greater frequency was also evident when B*27-positive patients and B*27- positive healthy controls were compared, although it did not reach statistical significance. No differences were observed in TAP2 alleles between the groups studied. DISCUSSION: We did not find a primary association between TAP2 polymorphism and AS susceptibility. Formal confirmation of a linkage between the TAP and HLA-B loci would probably require family studies.     

TAP polymorphism is not associated with ankylosing spondylitis and complications with acute anterior uveitis in HLA-B27-positive Japanese

Abstract: HLA-B27 is associated with the etiology of ankylosing spondylitis (AS) and acute anterior uveitis (AAU). Transporter associated with antigen processing (TAP) 1 and TAP2 polymorphism influences the range of peptide presented by HLA class I molecules. In this report, contribution of TAP polymorphism to the susceptibility to AS and AAU was studied in HLA-B27-positive Japanese individuals. Patients were classified into three groups: 16 AS patients, 14 AAU patients and 22 patients with both AS and AAU. Twelve HLA-B27-positive healthy individuals were included as a control. TAP polymorphism was detected by PCR-RFLP methods. Significant differences in frequencies of TAP1 alleles were not found between patient groups. None of the TAP2 frequencies showed increased or decreased frequencies compared with HLA-B27-positive healthy controls. In comparison with a random Japanese control, TAP2D allele frequency was significantly increased in the AAU group, but failed to reach a significant level in a group consisting of the AAU-only patients and the patients with both AS and AAU. All of the patient groups were noted to have a significantly increased prevalence of the TAP2H allele as compared to random controls; however, the higher frequency of this allele was detected in HLA-B27 healthy controls as well. These observations suggest a linkage disequilibrium between TAP2D, TAP2H and HLA-B27 in Japanese.     

Diversity of human leukocyte antigen-B27 alleles in Han population of Hunan province, southern China

This study was to investigate the frequency of HLA-B27 and its subtypes in the Han population of Hunan province, southern China. One hundred and sixty-nine healthy unrelated donors were tested for HLA-B27 by polymerase chain reaction-sequence-specific primer (PCR-SSP). One hundred and twenty-eight B27-positive spondyloarthropathy patients and 18 B27-positive healthy controls were subtyped using the high-resolution PCR-SSP. The phenotype frequency of human leukocyte antigen (HLA)-B27 was found to be 2.36% in healthy population. Five B27 alleles were identified: B*2704, B*2705, B*2706, B*2707, and B*2724. No significant difference was found in the distribution of HLA-B27 subtypes between the patients and controls studied. Notably, B*2724 was observed in a juvenile patient with ankylosing spondylitis. This subtype has not been previously reported in Chinese ankylosing spondylitis (AS) patients and other ethnic groups.     

Genetic polymorphisms of G protein-coupled receptor 65 gene are associated with ankylosing spondylitis in a Chinese Han population: A case-control study

ObjectiveThis study aimed to assess the association between two tag single nucleotide polymorphisms (SNPs) (rs68177277 and rs11624293) of G protein-coupled receptor 65 (GPR65) gene and ankylosing spondylitis (AS) susceptibility in a Chinese Han population.Methods673 patients with AS diagnosed according to the modified New York criteria and 679 age- and gender-matched healthy controls were recruited. SNP genotyping for rs68177277 and rs11624293 polymorphisms were performed using the SNPscan technique. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).ResultsGenotype and allele distribution of rs11624293 but not rs68177277 were significantly different between AS and controls (p = 0.004 and p = 0.002). Compared to the wild-type T/T genotype and T allele at rs11624293, the frequencies of C/T genotype and C allele were significantly higher in AS than controls after adjusting for age and gender (OR = 1.527, 95%CIs: 1.190–1.958; OR = 1.515, 95%CIs: 1.183–1.942, respectively). Dominant and co-dominant model of rs11624293 were predictive of AS susceptibility. In AS patients, the genotype of rs11624293 was significantly associated with BASFI scores in those with low disease activity (BASDAI < 4, p = 0.007).ConclusionsThe results of our study suggest that rs11624293 polymorphism of GPR65 gene is associated with the susceptibility and severity of AS in Chinese Han population.     

HLA-A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients

HLA-B27 is strongly associated to ankylosing spondylitis (AS). The objective of our study was to analyze HLA-B27 association, B27 subtype distribution and frequency of other HLA class I and DR antigens in a group of Basque AS patients. HLA class I antigens were typed serologically and HLA-B27 and A9 subtypes were determined by DNA typing in samples from 46 patients with AS, 54 B27-positive spondyloarthropathies, 82 healthy subjects and 20 B27-positive controls. A class I HLA 9.2 kb PvuII restriction fragment length polymorphism (RFLP), previously associated with AS, was analyzed in a representative group of patients and controls. We found that HLA-B*2705 conferred a relative risk of 126 for AS in this group. HLA-A9 (A*2402) allele was significantly increased in AS patients compared with healthy controls and B27-positive control group (Pcorr<0.0001) and also increased in patients affected with peripheral arthritis. No association between class I HLA 9.2 Kb RFLP and AS was found. These results suggest that HLA-A*9 allele itself or another linked gene could act as a secondary and independent susceptibility allele to AS.     

Tumor necrosis factor gene polymorphisms in ankylosing spondyiitis

Abstract: Despite the strength of the association of ankylosing spondyiitis (AS) with HLA-B27, other genetic elements could play a possible role in the pathophysiology of AS. In view of its gene location, in the proximity of the HLA-B locus, and biological effects, tumor necrosis factor (TNF) genes are potential candidates for additive susceptibility factors to AS. TNFα and TNFβ genotypes were analyzed by PCR-RFLP in 57 patients with AS, 102 random controls and 30 HLA-B*27-positive controls. No significant differences of TNFα promoter variations at position -308 and -238 were found in AS patients in comparison with controls. The -244 polymorphism was not detected in our population. The TNFβ genotype frequency was significantly different between AS patients and random controls. However, when the distribution of the TNFβ genotype was compared in B*27-positive AS patients and controls, these differences disappeared. In addition, we demonstrated that the TNFβ*l was in strong linkage disequilibrium with the B*27 allele, which may explain the differences observed for the TNFβ genotype among AS patients and random controls. Our data suggest that the polymorphisms of TNFα and TNFβ genes do not have an independent effect on AS susceptibility.     

GDF5基因rs224331多态性与汉族青少年体格发育指标关联分析

目的探讨中国汉族青少年GDF5基因rs224331位点多态性与身高、体重和BMI的相关性。方法采集江苏省某技校1790名17～22岁青少年的身高、体重指标并计算BMI。采用Taqman探针real-timePCR方法检测GDF5基因rs224331位点的单核苷酸多态性,并分析该基因位点与男女生身高、体重和BMI的相关性。结果 97.9%（1754/1790名）基因分型成功,男生859名,女生895名。rs224331位点频率最高的基因型为AA（51.7%）,其次为AC（39.6%）,CC最少（8.7%）。rs224331的基因型分布与男生、女生的身高无显著关联（P分别为0.728和0.723）;rs224331不同基因型间的男生体重和BMI差异均有统计学意义（P均〈0.01）,男生AC基因型体重和BMI均显著高于AA基因型（P=0.002）,女生中未发现类似的相关性（P分别为0.713和0.921）。结论 GDF5基因rs224331位点多态性在本研究的汉族人群中与身高无明显关联,提示该多态性位点可能存在种族特异性。rs224331位点多态性与男生体重和BMI存在相关性。     

Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients

Abstract
The HLA-B27 subtypes have a varied racial and ethnic prevalence throughout the world. However, the association of B27-subtypes with ankylosing spondylitis (AS) in the mainland China is unknown. To determine the association of B27-subtypes with AS in the Mainland Chinese Han population, a total of unrelated 153 patients with AS were enrolled in a large case-control association study, and 1545 unrelated, healthy, ethnically matched blood donors were included as controls. The genotyping of B27 and its subtypes was performed using the polymerase chain reaction with sequence specific primers (PCR-SSP). A total of 130 (84.97%) AS patients and 61 (3.95%) healthy controls were B27 positive. Three B27-subtypes, B*2704, B*2705 and B*2710, were further identified, of which both B*2704 and B*2705 were strongly AS associated. B*2710 was only detected in one AS patient and two other healthy controls. Considering only B27-positive cases and controls, a statistically different frequency of B27-subtypes was observed, with an over-representation of B*2704 ( P = 0.018). B*2704 was clearly more strongly associated than B*2705 with AS [odds ratio (OR ) = 2.4, P = 0.011]. Furthermore, a combined analysis including three previous studies of B27-subtype distributions in Chinese AS cases confirmed the stronger association of B*2704 with AS than B*2705 (OR = 2.5, P = 0.00094).     

湖南地区强直性脊柱炎患者中TNF-α-238位点的多态性研究

目的:通过分析湖南地区强直性脊柱炎汉族患者DNA中TNF-α-238位点的多态性,研究湖南地区汉族人群中TNF-α-238位点基因多态性与强直性脊柱炎发病的相关性.方法:应用聚合酶链反应-限制性片段长度多态性法( PCR-RFLP)对患者和正常人DNA中TNF-α-238位点进行基因分型检测,采用酶联免疫吸附法(ELISA)检测100例强直性脊柱炎患者和90例正常人血清中TNF-α的水平,HLA-B27分型采用流式细胞仪检测.用统计学方法分析两组中基因型、等位基因频率、TNF-α水平、HLA-B27阳性率及其组间差异.结果:100例患者中TNF-α-238位点G/G基因型95例(95%),G/A基因型5例(5%),90例正常人中TNF-α-238位点G/G基因型88例(97.8%),G/A基因型2例(2.2%).AS组的TNF-α-238位点G频率(97.5%)低于正常对照组(98.9%),A频率(2.5%)高于对照组(1.1%);两组均未发现A/A基因型;AS组患者血清中TNF-α的平均水平比正常人明显增高[(10.16±1.19) pg/ml vs.(5.64±1.18) pg/ml],且G/A基因型患者血清中TNF-α的平均水平比G/G基因型患者高[(13.49±1.27) pg/ml vs.(9.44±1.29 pg/ml)];HLA-B27阳性率在湖南地区AS组和正常对照组中的分布差异极其显著(χ~2=114.975,P=0.000).对 HLA-B27和TNF-α-238两位点的基因分析表明,与单独HLA-B27阳性比较,TNF-α-238位点基因型为G/G时比数比(OR值)明显增加.结论:湖南地区汉族人群中TNF-α-238位点多态性与强直性脊柱炎发病可能没有相关性,但基因型为G/G时AS的患病风险可能增高.     

Association of HLA genes with ankylosing spondylitis in Han population of eastern China

Ankylosing spondylitis (AS) is a chronic inflammatory disorder with a multifactorial genetic basis. HLA-B27 was reported with the greatest susceptibility to AS but did not act alone. The aim of this study was to search for other gene(s) associated with AS independently of HLA-B27 using 13 microsatellite markers spanning 1.5 Mb from locus TAP1 to HLA-Cw and a single-nucleotide polymorphism marker within NFkappaBIL1 gene promoter. Genotyping for microsatellites was performed in 175 AS patients of eastern Chinese and 219 ethnically matched healthy controls using polymerase chain reaction with fluorescence-labelled primers, whereas the SNP marker was genotyped by direct DNA sequencing. Allele as well as haplotype frequencies were compared between cases and controls, and a linkage disequilibrium analysis was performed to estimate the LD relationship between the candidate regions. The frequencies of alleles D6S2811*128, STR_MICA*A5.1 and D6S2672*109, as well as haplotypes D6S2811*128-D6S2927*213-D6S2810*340, D6S2927* 221-D6S2810*350-MICA*A5.1, and D6S2810*350-MICA*A5.1-D6S2800* 136 were significantly increased in B27-positive AS patients when compared with B27-positive controls. The results indicated that there may be other gene(s) within the HLA region, especially around locus HLA-B or HLA-Cw, with susceptibility to AS independently of HLA-B27.     

Sex-specific Association of the Zinc Finger Protein 259 rs2075290 Polymorphism and Serum Lipid Levels

Background: Little is known about the association of ZNF259 rs2075290 single nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population. This study aimed to detect the association of ZNF259 rs2075290 SNP and environmental factors with serum lipid levels between males and females in the Mulao and Han populations.Methods and Results: Genotyping of ZNF259 rs2075290 SNP was performed in 788 of Mulao and 778 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequencies were significantly different between Mulao and Han populations (AA, 50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P = 0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05-0.01) but not in Mulao''s.Conclusions: The subjects with AG/GG genotype in Mulao males and females and Han females have less favorable lipid profiles than those with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have more favorable lipid profiles than those with AA genotype. These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity.     

HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility

Characterization of non-B27 susceptibility genes will be required to know the pathogenesis of AS. The aim of this study was to examine whether ankylosing spondylitis (AS) susceptibility is controlled by B27 alone rather than B27 haplotypes and, whether other closely related class I loci, such as MICA and TNFA genes might play a role in AS. Three hundred eleven B27-positive samples from Caucasoid, Asian, and African populations were selected and genotypes were carried out by PCR/SSOP (HLA-B27 and HLA-C), PCR/SSP (MICA-TM polymorphism in the transmembrane region), PCR/SSCP (MICA alleles), and PCR-RFLP (TNF-alpha). Of these, 161 were AS patients, chosen in order to investigate the contribution of TNFA and MICA loci to AS in HLA-B27 positive individuals. Some findings can be concluded from the study: (a) No significant differences of TNF-alpha promoter alleles at position -308 and -238 (A/G) were found between AS patients and B27 matched alleles from healthy controls; (b) strong linkage disequilibrium was found between the B27 and the MICA alleles. The MICA-A4 was found to be in association with B*2705,02,03 and 08; MICA-A5 with B*2704 and B*2707 and MICA-A.5.1 with B*2706; (c) no significant differences of MICA alleles were found between AS and controls carrying the B27-associated alleles, and therefore no evidence is provided for an additional role of MICA gene in AS susceptibility; (d) there are a striking correlations between the structure of B27 extended haplotypes (from MICA region to HLA-C) and the ethnic distribution of these subtypes. The results of differential linkage disequilibrium with HLA-B27 subtypes suggest that B27 itself remains the primary gene for AS susceptibility, and TNFA and MICA are not involved in the pathogenesis of the disease.     

TAP1 and TAP2 polymorphism in HLA-B27-positive subpopulations: no allelic differences in ankylosing spondylitis and reactive arthritis

The polymorphic TAP1 and TAP2 genes encode subunits of the transporter that delivers peptides to the HLA class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We studied TAP1 and TAP2 polymorphism in two multifactorial HLAB27-associated diseases, ankylosing spondylitis (N = 30) and reactive arthritis (N = 30), in order to establish whether TAP genes are involved in the different pathogenesis of these diseases. Healthy HLA-B27-positive individuals (N = 55) were chosen as the primary controls and 93 individuals represented the random Finnish population as secondary controls. We found differences between the random and HLAB27-positive populations, thus suggesting that certain TAP alleles are prevalent in HLA-B27 haplotypes. No differences were found between the AS and ReA groups nor between either of them and the healthy HLA-B27-positive controls. Thus it seems unlikely that TAP polymorphism, at the level studied, has a dominant role in the pathogenesis of these diseases. However, a family study is needed in order to determine whether the same TAP complexes are carried by the same haplotypes in these diseases. Human Immunology 44, 236–242 (1995)     

辽宁汉族人群HLA-B等位基因多态性的分布

目的调查辽宁汉族人群HLA-B等位基因的遗传多态性。方法用聚合酶链反应．序列特异性引物方法对辽宁8962名健康无关汉族人进行HLA-B等位基因分型，计算HLA-B等位基因频率并与不同人群HLA-B等位基因的多态性进行比较。结果共检出HLA-B等位基因34种，其中B＊15（14．42％）、B＊40（14．33％）和B＊13（11．99％）基因频率分布较高，B＊82、B＊83等位基因未检出；HLA-B座位特异性49种。该人群与南北方汉族人群、日本人、黑人和白人分别进行X^2检验差异有统计学意义，X^2值分别为1584．799、72．145、1393．339、7406．288和5311．947。结论辽宁汉族人群HLA-B基因多态性分布有其自身特点，它的遗传特征不同于既往的南、北方汉族。     

Polymorphisms of KIR Gene and HLA-C Alleles: Possible Association with Susceptibility to HLA-B27-Positive Patients with Ankylosing Spondylitis

Accumulating evidences indicate that killer cell immunoglobulin-like receptors (KIRs) and their corresponding specific HLA-C ligands contribute to the pathogenesis of multiple autoimmune diseases via the modulation of natural killer (NK) cell and T cell functions. The present study was performed to investigate whether the polymorphism of KIR genes and HLA ligands associates with the susceptibility of ankylosing spondylitis (AS). Previous studies have demonstrated a strong association between HLA-B27 gene and the pathogenesis of AS. In this study, 115 unrelated HLA-B27-positive AS patients and 119 HLA-B27-positive healthy controls were recruited. Polymerase chain reaction using sequence-specific primers was used to determine the genotypes of KIR genes and HLA-C alleles. The results showed that the frequencies of KIR2DL1 and KIR2DL5 were significantly higher in the AS patient group than those in the control group (p = 0.012 and p = 0.009, respectively). Meanwhile, individuals with AS showed an increased frequency of HLA-Cw*08 (p = 0.001, p _c  = 0.008) compared with that in controls. Our findings indicate that with the genetic background of HLA-B27, variation at the KIRs and their corresponding specific HLA-C ligands may influence the ability of NK cells and T cells to recognize and lyse targets in immune responses, which thereby contributes to pathogenesis of AS.     

A functional polymorphism of the vasoactive intestinal peptide receptor 1 gene correlates with the presence of HLA-B*2705 in Sardinia

The association of HLA-B27 with ankylosing spondylitis (AS) is the strongest among all inflammatory diseases. However, the exact role of these molecules in disease pathogenesis is still unknown. The existence of HLA-B27 variants rarely found in patients introduces a further level of complexity. It is now accepted that other genes of minor impact contribute to modify disease susceptibility and these genes might be diverse in different populations depending on the genetic background. We report here a study performed in Sardinia, an outlier population in which two major HLA-B27 subtypes are present, B (*)2705 strongly associated with AS and B (*)2709 which is not, and show the co-occurrence of the B (*)2705 allele with a single nucleotide polymorphism (SNP) mapping at 3'-UTR of the receptor 1 (VIPR1) for the vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties. This same SNP is associated with a different kinetics of down-modulation of the VIPR1 mRNA in monocytes after exposure to lipopolysaccharide (P=0.004). This particular setting, HLA-B (*)2705 and a functional polymorphism in VIPR1 gene, might be due to a founder effect or might be the result of a selective pressure. Irrespectively, the consequent downregulation of this receptor in the presence of a 'danger' signal might influence susceptibility to AS.     

MICA gene and ankylosing spondylitis: linkage analysis via a transmembrane-encoded triplet repeat polymorphism

In order to address the possibility that the MICA gene located 47 kb upstream from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we have investigated microsatellite polymorphism in the transmembrane region of MICA in Caucasian patients with AS. The microsatellite allele consisting of 4 repetitions of GCT/AGC was present at significantly higher frequency in the patient group (Pc<0.0000001) than in the ethnically matched control group. However, the frequency of the (GCT/AGC)₄ allele was significantly low in the B27-positive patients than in the B27-positive healthy controls (Pc=0.0145). These observations suggest that B27 itself remains the primary genetic marker for AS, although the significantly dissimilar pheno-type frequency of the (GCT/AGC)₄ allele in B27-positive patients and healthy individuals may reflect the existence of other genetic factor(s) in the HLA-B27 haplotype involved in the development of AS.     

Sex-specific association of the peptidase D gene rs731839 polymorphism and serum lipid levels in the Mulao and Han populations

Little is known about the association of peptidase D (PEPD) gene rs731839 single nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese population. The objective of the present study was to detect the association of the PEPD rs731839 SNP and serum lipid levels in the Mulao and Han populations. Genotyping of the PEPD rs731839 SNP was performed in 751 subjects of Mulao and 762 subjects of Han using polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. The A allele carriers had higher serum high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI levels and lower triglyceride (TG) levels in Mulao; and higher HDL-C, low-density lipoprotein cholesterol (LDL-C) and ApoAI levels in Han than the A allele non-carriers. Subgroup analyses showed that the A allele carriers had higher HDL-C, ApoAI levels and lower TG levels in Mulao males but not in females; higher total cholesterol (TC), HDL-C, LDL-C and ApoAI levels in Han males; and higher TG, HDL-C and ApoAI levels in Han females than the A allele non-carriers. Serum lipid parameters were also correlated with several environmental factors in Mulao and Han populations, or in males and females in both ethnic groups. The association of the PEPD rs731839 SNP and serum lipid levels was different between the Mulao and Han populations, and between males and females in the both ethnic groups. There may be an ethnic- and/or sex-specific association of the PEPD rs731839 SNP and serum lipid levels in our study populations.     

Sex-specific association of the SPTY2D1 rs7934205 polymorphism and serum lipid levels

The objective of the present study was to detect the association of the rs7934205 single nucleotide polymorphism (SNP) near the Suppressor of Ty, domain containing 1 gene (SPTY2D1) and serum lipid levels between males and females in the Mulao and Han populations. Genotyping of SPTY2D1 rs7934205 SNP was performed in 933 of Mulao and 865 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The T allele frequency was different between Mulao males and females (23.2% vs. 27.9%, P = 0.018). The genotype and allele frequencies were also different between Han males and females (P = 0.020 and P = 0.004; respectively). Serum levels of apolipoprotein (Apo) A1 in Mulao males; and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ApoA1 and ApoB in Mulao females were different between the CC and CT/TT genotypes (P < 0.05). Serum TC, ApoB levels in Han males, and ApoB levels in Han females were different between the CC and CT/TT genotypes (P < 0.05). The subjects with CT/TT genotype in both Mulao and Han males and females have more favorable lipid profiles than those with CC genotype. These findings suggest that the association between the SPTY2D1 rs7934205 SNP and serum lipid levels might have ethnic- and/or sex-specificity.